NOTE: This spoiler sent in by Rahul.
Beverly Hills. We see many shots of rich people with their pedigreed pooches around the trendiest parts of town. Chloe, a spoilt Chihuahua with little pink booties, is brought into a pet boutique by her owner, Viv (Jamie Lee Curtis), in a Louis Vuitton bag, much to the envy of the other dogs. She's got real diamonds in her collar. Chloe speaks (in dog-tongue) to the other dogs. Her owner, Viv, heads Vivacity Cosmetics. Chloe is then taken to a high-end pet clothing store.
At home, we meet Papi (George Lopez), Sam the landscaper's (Manolo Cardona) Chihuahua, who digs holes for his owner. He tries flirting with Chloe during his break, but she blows him off, though that only makes him try harder. Viv's niece, Rachel (Piper Perabo), comes to visit. She and Chloe don't seem to like each other at all. Viv is on her way to Europe to promote her cosmetics line and can't take Chloe (as Chloe hates Berlin) and their dog-nanny just gave birth. Not wanting to leave Chloe with strangers, she entrusts Chloe in Rachel's care. Neither Chloe nor Rachel is thrilled.
As Viv leaves, she gives Rachel Chloe's schedule and leaves. Soon, three of Chloe's friends are brought over for a playdate. She has to attend to the dogs, including pouring them chilled Evian by the pool. Rachel's friends are also there, lounging by the pool. Chloe and Rachel complain to their friends about the other. Rachel says Chloe's spoilt rotten. Chloe says Rachel's an irresponsible loser. Papi shows up and "protects" Chloe from a "dangerous" pigeon, by chasing it away, jumping over Rachel and her friends. Rachel goes to complain to Sam. Papi tries his luck with Chloe again, but to no avail. Sam calls Papi over. He seems to like Rachel.
The next morning, Chloe tries to wake Rachel up for a mani-pedi, but Rachel only wakes up when her phone rings. Her friends invite her for a road trip to Mexico, and she takes Chloe along. While the three girls ride through town, taking in the sights, Chloe wonders if there's a Four Seasons in this place. They check into a hotel. Chloe impatiently waits for her dinner, while Rachel and her friends plan to go for a party. Rachel finally places a bowl of dog-food in front of her, far from the prime rib Chloe expects. She gets revenge by placing a big morsel of the dog-food in Rachel's shoe. Rachel yells at Chloe, but Chloe pretend-limps, making Rachel's friends think she hit Chloe. The girls leave, leaving Chloe behind. In no mood to stay home, Chloe distracts the hotel manager and sneaks out, albeit quite conspicuously.
She walks around town, looking for Rachel. She finds her at a party, but is suddenly abducted by a dognapper, who puts her in his van along with other dogs. Returning home, Rachel freaks out when she discovers that Chloe's missing. The next day, she goes to look in an animal shelter. The lady there tells her that some dogs are stolen to participate in dogfights, which take place in Mexico City. She tells her friends that she plans to look around more in town and then maybe head to Mexico City.
Meanwhile, in Mexico City, Chloe is placed in a not-so-luxurious cage. A German Shepherd nearby named Delgado (Andy Garcia) sourly tells her she's in the dogfights. She whines a bit, but another dog, Rafa (Eddie 'Piolin' Sotelo), tells her she won't be getting any sympathy from Delgado as he's a gladiator - the best of the best. However, some other dogs disagree, saying El Diablo is the best. Chloe whines, but Delgado tells her that she might be ransomed, which cheers her up a bit.
Meanwhile, in Beverly Hills, Papi comes back, looking for Chloe, but can't find her. He runs inside the house and finds Rachel's friend, Angela, looking through some pictures. Sam comes in and busts Angela with the pictures. She comes clean about Chloe's disappearance. She needs to email Chloe's picture to Rachel in Mexico City. Papi is shocked at the news.
In Mexico City, a dogfight is underway. First, the crowd favorite, El Diablo (Edward James Olmos), is introduced. He's a mean mother... I mean, Doberman. And his opponent is... Chi-Chi-Huahua, better known to us as Chloe. The spectators laugh at Chloe and clap. At first believing they're actually cheering for her, she runs into a snarling El Diablo. She tries to talk her way out of it, but El Diablo is having none of it. Inside the cages, Delgado sympathizes with Chloe, and busts out of his cage. He sets free all the other dogs, and they run, while he runs towards the ring. In the ring, El Diablo rips off Chloe's little doggie-sweater, exposing her diamond collar. The dognapper, Vasquez, sitting above everybody, notices it. Chloe tries to claw her way under the gate, as El Diablo menacingly approaches. Delgado manages to open the gate, letting Chloe through, and closing it before El Diablo can get through. As they run away, El Diablo barks at Delgado that he will find them.
The dogs run off into the night. Vasquez orders his goons to catch the Chihuahua. The dogs run into an open-air market, with the dognappers in hot pursuit. Chloe drops her bootie and almost goes back for it, but Delgado pulls her away. They manage to get away, by jumping over a chain-link fence. Vasquez orders his goons to find Chloe, as she must be worth a lot of money, judging by her diamond collar. He puts a collar with a GPS on El Diablo and tells him to find Chloe. El Diablo runs off in pursuit.
Meanwhile, Delgado and Chloe happen by a Day of the Dead parade. Delgado takes his leave. She follows him, but he tells her that it's every dog for itself. He agrees to take her to the Carthay Hotel (where Viv and Chloe are preferred guests). As they run, they hear El Diablo's howl. Delgado, knowing that he is following Chloe's scent, dunks her in a puddle of muddy water.
Meanwhile, Rachel speaks to a harried Detective Ramirez (Jes˙s Ochoa) at the local police station in Mexico City. He tells her that they've tried unsuccessfully to stop the dogfights. He asks her to get him the picture of Chloe. Rachel gets a call from Viv, calling from Capri. She asks to speak to Chloe. Rachel mimics Chloe's "arf" several times, standing in the police station, much to the bewilderment of the personnel there.
Chloe and Delgado reach the Carthay Hotel. Asking him to stay outside, he goes inside and barks at the concierge to give her a room. However, she's shown the door. When she sees her reflection, she sees what a mess she is. Meanwhile, Delgado goes to check what's taking her so long. Looking through the restaurant window, he sees a Chihuahua sitting with its rich owners. Thinking it's Chloe and feeling a bit betrayed, he leaves. Chloe comes out, whining, but doesn't see Delgado there. Feeling all alone, she walks around town. Finally, she curls up under a park bench and sleeps.
The next morning, Rachel goes to the police station to speak to Ramirez. She notices Sam and Papi there. Sam's there to look for Chloe as well. They speak to Ramirez about Chloe's diamond collar. He promises to forward the "missing canines report" to other stations and tells them to leave the police work to the cops. However, Rachel wants to keep looking, and so does Papi. Papi runs after Rachel, prompting Sam to follow.
When Chloe wakes up, she sees a Churro left behind by a nice kid and runs to eat it. However, she's confronted by a pack of street dogs, who want the Churro for themselves. However, she goes into a tirade of her ordeal and snarls at them not to push her. They run off, tails between their legs. However, they weren't scared of Chloe, but of the huge scary El Diablo behind her. However, Delgado comes to her rescue again, grabbing Chloe and running off. El Diablo gives chase. They run into a museum, past the people and hide in an exhibit. El Diablo bursts in and, while the guards have their hands full with him, they run off. Delgado tells her that they're going to Puerto Vallarta, as somebody there can help them.
They stow aboard a truck. She asks why El Diablo is after her. He guesses that Vasquez must have sent him. The cops have been after Vasquez for a long time, but haven't been able to catch him. She tries asking more questions about Delgado's past, but he ignores her. Just as the truck pulls away, Papi shows up, with Rachel and Sam behind him. Papi finds one of Chloe's booties and shows it to Rachel. However, unbeknownst to them, one of Vasquez's goons watches them. He calls Vasquez and reports that there are others looking for Chloe. Vasquez, now aware of Chloe's owner, Vivian Ashe, tells him to find Chloe first.
In Puerto Vallarta, Delgado tells her to stay near a fountain, while he goes to "see a man about a dog" (or the other way around). Chloe takes a refreshing bath in the fountain. A pack rat, Manuel (Cheech Marin), and an iguana, Chico (Paul Rodriguez), seeing her, plan to con her. Manuel gets in Chico's mouth, as if the latter was eating him, and yells for help. Chloe comes along and shoos away Chico. Manuel sees the diamond collar and asks where Chloe's from. She replies Beverly Hills. He tells her that he's a porter in a cruise ship, who tends to upscale dogs like Chloe. Staring hungrily at the collar, he promises to get her home.
Delgado reaches the police dog training ground and watches nostalgically as the dogs are trained. One of the police dogs, Tomas (Carlos Juvera) sees him and goes over to him. They seem friendly. Delgado tells Tomas that he's doing a private security thing, escorting a rich Chihuahua to Beverly Hills. However, Vasquez is after them and so is El Diablo. Tomas asks him if that's why he's doing it, but Delgado says it's just a job. He needs an officer to run Chloe's collar tag. Tomas tells Delgado to bring Chloe.
When he returns to the fountain, he sees that Chloe's collar is missing. Cheerfully, she tells him that she handed it to Manuel (who she saved from an iguana) to show to a ship captain for him to read the tag. Delgado yells at her, saying that iguanas are vegetarian and that this is the oldest con in the book.
Wearing the diamond collar, Manuel and Chico gloat over their latest con, when they're confronted by El Diablo. He demands to know where the Chihuahua is. Manuel tells him and El Diablo runs off.
Delgado takes Chloe to a railyard, to meet a Coyote, a smuggler that sneaks collarless dogs across the border. She infers that Delgado was a police dog and asks why he no longer is. He just says that he did something wrong. When she persists with the questions, he yells at her to stop. He puts her on a train to Tijuana. The Coyote (Ed Francis Martin) will take her to America after that. As the train starts, she watches tearfully as Delgado walks away. However, he gets a change of heart and runs for the train. After a really fast run, he manages to get on the train compartment. As they travel, unknown to them, El Diablo jumps on the train.
While Rachel and Sam ask people about Chloe, Papi gets her scent and runs towards some sewage pipes, where Chucho (Luiz Guzman) and Rafa lie. He says that they have Chloe's scent and describes Chloe. They remember Chloe from the dogfight. Papi tells them to follow him and leads them to Rachel and Sam. Rachel is all for keeping them, as long as they give them a bath as they stink. After an eventful doggie-bath, the two fresh dogs speak to Papi about their quest. He refuses to give up.
The next morning, Sam tells Rachel that Ramirez has reported that Chloe and a German Shepherd were seen in Puerto Vallarta.
In a store, Manuel and Chico are discovered inside the piñata they were hiding in. After a funny chase, they manage to get away from the broomstick-wielding owner, but drop the diamond collar, which the owner keeps.
In the train, Delgado is discovered and runs amuck, pursued by the train crew. He jumps out onto the ground. Chloe jumps out as well, right on his back. She doesn't want to leave him. However, they now have a long walk ahead of them.
Ramirez, Rachel and Sam speak to the store owner about the collar. Apparently, he was almost arrested for having it. He complains about the rat and iguana. Rachel gives him Chucho, much to his pleasure. Rafa and Chucho say goodbye to each other. Ramirez tells Sam and Rachel about the canine-related incident on the train, near Puerto Vallarta. They plan to go there. Manuel and Chico, wanting the collar back, sneak into Sam's car. Sam, Rachel, Papi and Rafa head for Puerto Vallarta.
Chloe and Delgado find themselves lost. Chloe discovers that Delgado has lost his sense of smell. That's why he's no longer in the police force. They hear mountain lions roaring in the distance. They hide in a cave. He tells her his story. He was on point in a drug bust. However, his partner was attacked by El Diablo and wounded badly. The next day, he couldn't smell - a psychological thing. Suddenly, the mountain lions attack and Delgado tries to fight them off. They are interrupted by a cloud of dust approaching fast. The cloud of dust settles and it’s a large pack of angry-looking Chihuahuas. The mountain lions tuck tail and run. The head of the pack, Monte (Placido Domingo), tells Chloe and Delgado to follow them. They reach Chihuahua, their birthplace. They walk through the Chihuahua-filled place. That night, there is a big celebration. Monte goes into a tirade, speaking of how Chihuahuas are seen as lapdogs or toys. The Chihuahuas bark "No more!" They are tiny, but mighty. They start to bark out, however, Chloe's bark is too embarrassingly high-pitched. Monte tells her that her bark will come when she needs it the most.
Sam, Rachel, Papi and Rafa reach Puerto Vallarta and stay with an old widow. In the car, Manuel and Chico bust out of Rachel's suitcase and start looking for the collar. Papi catches them. They tell him about El Diablo. El Diablo runs along the tracks, following Chloe's scent. Vasquez and his goon, Rafferty, not as gifted, follow him through the GPS tracker on his collar.
Chloe and Delgado prepare to leave Chihuahua. Monte says goodbye. Chloe seems to miss Papi. They go into a restaurant and see a sign with Chloe's picture. Chloe realizes Rachel's looking for her. They bark and get the attention of two cops, who recognize Chloe from her picture.
Sam and Rachel give Rafa to the old widow. Just then, Sam tells Rachel that Ramirez called saying that's Chloe's found. They go to the police station where Chloe and Delgado are. A cop is taking Chloe behind the bushes at the moment. Vasquez and Rafferty arrive in their van. Papi, in the car, notices Vasquez and gets Chloe's scent from the van. He jumps out of the car, and heads to where the van is parked. Manuel and Chico look for the collar.
Behind the bushes, El Diablo attacks Chloe. Delgado notices Vasquez and realizes that Chloe is in trouble. He gets loose from the leash and runs towards the bushes, but can't find Chloe anywhere. El Diablo takes Chloe to Vasquez's van. Vasquez tells Rafferty to put Chloe inside the van. Just as he opens the door, Papi bites him in the nose. Papi and Chloe run up an Aztec structure, followed by El Diablo. Chloe falls through the decrepit floor as it crumbles.
Manuel and Chico manage to get out of the car, with the collar, but are stopped by Delgado. Manuel offers Delgado the collar so he can follow Chloe's scent. At first, Delgado says he can't, but suddenly he gets Chloe's scent. He takes the collar to the people. Sam, Rachel and the cops follow him. He leads them to the Aztec structure.
Vasquez, Rafferty and El Diablo look for Chloe. Papi is caged, though his razor-sharp tongue can't be caged as easily. Chloe hides from them, although El Diablo has her scent. Delgado happens by and sees El Diablo. He gives out a high-pitched Chihuahua bark, getting the villains' attention. Rafferty runs towards it and is arrested by the cops. Chloe comes out of hiding and gets Papi out of his cage. However, they are spotted. Vasquez chases after Chloe, while El Diablo chases after Papi. She stands on a ledge, while Vasquez tries to catch her. El Diablo has Papi cornered. Chloe shouts out "No more!" and lets out a ferocious bark, scaring both El Diablo and Vasquez. They take to their heels. Vasquez is tackled to the ground by Delgado and arrested by the cops.
Chloe, proud of her bark, rejoins Papi. However, El Diablo confronts them. Delgado attacks El Diablo, but the latter pushes him off. Chloe jumps on El Diablo's back. He runs around and finally knocks her off, but gets hard-tackled by Delgado. He manages to get away though. However, Chloe is on the ground, not moving, while Papi stands near her and pleads lovingly for her to get up. She wakes up, but keeps still so he can keep talking. She finally gets up, much to his relief. Sam and Rachel come running up. Ramirez pats Delgado on the head. Chloe and Rachel have a happy reunion.
While the dognappers are taken away, the dognapper-nappers (the dogs) watch. Delgado starts to leave, but Chloe tries to stop him, saying they need a guard dog. Delgado says he has to go after El Diablo. Chloe can take good care of herself now. He's sure they'll be seeing each other again. He starts to walk off. Rachel speaks to Ramirez and he calls Delgado and gives him back his police collar. Delgado couldn't be happier. Rachel, Sam, Chloe and Papi leave. Chloe and Delgado thank each other.
They reach Viv's Beverly Hills mansion. Viv is expected back anytime soon. Just as Rachel and Chloe run inside, Viv's car pulls up. Sam tries to stall her, but she really wants to see Chloe. Rachel runs downstairs and hugs Viv. Just then, Chloe also comes downstairs, looking and dressed like nothing happened.
While Chloe and Papi sit in the gazebo, Rachel asks Sam out. The movie ends with Chloe licking Papi's face.
While the credits roll, Papi lets us know that Delgado captured El Diablo and got a medal. El Diablo was then adopted by a rich lady, who likes to dress up her pets. Rafa is a spokesmutt for a doggie-toothpaste. Chloe's rich doggie friends have their own reality dance show. Manuel and Chico are in Beverly Hills. Papi and Chloe have quite a litter.