The movie starts with a kid named Josh (Jonathan Tucker) wandering through a college campus. He keeps glancing behind him, as though he is being followed, but never sees anyone, though he does occasionally catch glimpses of a very pale figure behind him in mirrors and security monitors and such. He heads into the campus library and starts calling out for someone named Ziegler, but doesn't find him. While he's searching, the lights start going out one by one, but then come back on. We see a shimmering behind him, but when he turns to look, nothing is there. Suddenly something starts pushing some books off of a spot on a nearby bookshelf. Josh goes to check it out, looks into the hole, and is knocked flat by the pale figure, who leaps through the hole and lands on top of him. Josh screams, and the pale figure starts absorbing him.
Meanwhile, we see Josh's girlfriend Mattie (Kristen Bell) at a bar doing some late night partying with her friends Isabel (Christina Milian), Stone (Rick Gonzalez), and Tim (Samm Levine). Mattie laments to her friends about how lately her relationship with Josh has degenerated into a relationship with each other's voice mail, and the others try to cheer her up through dancing, heavy drinking, and dirty cell phone pictures. It doesn't take, though, and eventually Mattie heads back to the dorm she shares with Isabel. Once there, she finds two messages -- one from her mom asking to call her, and one from Josh where he tries to say something, but just gives up. Mattie tries to call him back, but the phone just rings in his apartment, and Josh doesn't bother picking up. Four hours later, Mattie tries again and gets the same response. She goes to sleep and the next day heads off to class, where the instructor is talking about the various forms of stalking when Isabel interrupts by arriving late and with coffee. She heads to a seat and texts a message to Mattie -- "Wake me when its over" -- which just makes Mattie look back at her and shake her head.
Later, Mattie and company are talking about the absent Josh and she decides to head over to his apartment and check up on him. When she gets there, she notices that one of his windows has a red light coming out of it. She heads up to his apartment and uses the spare key to get in. Once inside, she sees that everything is a complete disaster, with clothes unfolded, dishes unwashed, and food being left out and crawled over by maggots and cockroaches and the like. She finds Josh, but he is completely listless and doesn't seem to care much about anything. He tells her to hold on a sec, takes his mouse, and goes into his bedroom. She waits and hears a scratching coming from the closet. She opens the door and finds Josh's cat, starved and with hair falling out. She screams and goes to find Josh, noticing an active program on his computer that seems to be a bunch of numbers running constantly. She opens the bedroom door and finds that Josh has hung himself. Later, she is in a police car and calls her mom. She gets the voicemail and asks her mom to call her, since she really needs to talk to her, though she doesn't say why. Outside, Mattie sees Isabel looking for her. She gets out of the car and the two hug, and Isabel consoles Mattie.
Some time after this, we see Mattie walking through Josh's apartment. He starts telling her to watch out and to be careful just before something attacks her. She screams and wakes up, realizing that it was just a nightmare. Later that day, we see her at a shrink. The shrink, Dr. Waterson (Ron Rifkin) is trying to get her to open up, but she isn't having it. Eventually, she breaks and starts crying. Waterson tries to tell her that it's okay, but she gives up on him and storms out. Outside, she hooks up with Isabel and the two head back to their dorm. That night, we see Mattie chatting online with Tim and Stone, who are trying to make her feel better, when suddenly they all start getting messages from Josh saying "Help me". They meet up the next day and eventually Stone says he'll go and unplug Josh's computer, since that must be the reason they're still getting the message (it's still logged on). He heads over there and unhooks the computer and starts looking around. In the bedroom he sees another computer with the words, "Do you want to see a ghost?" on it. He clicks on the words and sees an image looking straight at him. He looks up and sees a shimmering in the air just before a pale figure starts walking towards him. He screams and jumps backward into another room where every surface is covered with red tape. He trips over the bed and hides behind it for a minute. He looks underneath it and doesn't see anything. He then looks up and sees the pale lady looking down at him. He screams and gets absorbed by the figure.
The next day, we see Isabel and Mattie getting their mail when they find a package in it from Josh that is postmarked two days before he died. The girls meet up with Tim in a computer cafe and find that the package contains three rolls of red tape and a note that says , "It keeps them out -- don't know why." They try to call Stone and ask where he is, but when he picks up all he says is that he's feeling down and won't be joining them. After he hangs up, we see him pull down a sleeve and look at his arm, which has a strange black growth on it that is actively spreading. Back with the others, we see Mattie saying that when she spoke to Stone, she got the same feeling that she did when she was talking to Josh before he killed himself, although she can't quite describe the feeling. She tells them about what she saw on Josh's computer and decides to go and try and look at it the next day. However, when she does go to look, she finds that the whole apartment has been emptied out of Josh's stuff and everything thrown out. After talking with the cleaning lady, Mattie finds out that the computer has been sold. Fortunately, she is able to get an address out of the woman for the guy she sold it to. She also gets the name of the guy -- Dexter McCarthy.
A while later, we see Dexter (Ian Somerhalder) working on his car when Mattie comes up and starts asking why he's messing around with the people on Josh's buddy list. After telling her she's crazy and working through the confusion, he shows her the computer -- unplugged and still in his car trunk. Later, we see Dexter at the now assembled computer. He turns it on and starts seeing images of various gray people doing stuff which would ultimately result in them being killed. Meanwhile, we see Mattie on a bus that is headed back to her dorm when she sees one of the gray people reflected in a mirror behind her. She turns around but naturally doesn't see anyone. She faces forward again and sees her psychology professor walking across the street rather slowly. The bus honks at him and he starts walking toward it. The bus narrowly misses him, and we later see Mattie telling Tim and Isabel about this as a TV in the background relates the story of a suicide epidemic that is apparently taking place throughout the city. Mattie moves to leave, but is interrupted by Dexter, who has apparently found something and needs to show it to her. Back at his place, he shows her the images of the dead that he found, but she freaks out and leaves. Later, we see Mattie taking a bath when one of the doors closes itself. She moves to look and suddenly sees one of the grey people underneath the water. She screams and tries to get out, but a second later a sponge pops up from underneath where the gray person's face was.
The next day, after taking a psychiatry test with two other people in a nearly empty lecture hall, we see Mattie taking a bathroom breather. She goes to sit down on one of the toilets when she hears something outside. She bends over to look, but doesn't see anyone. She leans back and hears someone in the next stall, and we see one of the gray people in it. Mattie gets up and goes to wash when the stall she was just in swings shut. She cautiously goes to look and opens the door, but no one is there. Mattie goes to visit Dr. Waterson again. She tries to convince him that the gray people are real, but he naturally doesn't believe her and instead says that they are mental demons that she must exorcise or succumb too (well he's half-right, anyway). Meanwhile, we see Tim over at Stone's dorm looking for him. He goes into the room and doesn't find anyone. He sees the computer is on and after waking it up, sees the screen that says, "Do you want to see a ghost?" He clicks it and sees Stone looking at him from the computer screen. He jumps back and sees Stone behind him, screaming that he doesn't want to die as he is absorbed into the wall by the black stuff. Tim screams and runs for his own dorm room. He immediately covers every crack he can find with red tape when he hears someone outside. He slowly moves to look through the peephole....and is instantly overtaken by the grey person that was outside.
That night, we see Dr. Waterson working late in his office when his computer goes black. He clicks the mouse a couple times and suddenly a woman can be seen on it. His eyes go down to a picture on his desk, and we realize that the woman is his late wife. Just then, a shimmer is seen in front of his desk and before he can do anything, a gray person takes him. Meanwhile, we see Mattie trying to get to sleep when her printer starts spitting something out. At first she can't make out anything coherent, but then another sheet comes out, followed by another, and another....eventually she puts all the sheets together on her floor and sees the face of a grey person. She heads for Dexter's loft where he shows her something he found on Josh's hard drive -- a set of video diaries and communiques, which start with him asking a guy named Ziegler (the one he was looking for before) why he won't talk to him, and end with him describing how he just doesn't care about anything anymore and apologizing to Mattie. Shaken, she and Dexter go to an all-night diner and talk about what they know, but they get interrupted by an old crackpot who overhears them and says that everything they've seen means that the end of the world is upon them.
While Dexter and Mattie are out, we see Isabel heading downstairs to do her laundry. After briefly chatting with another girl, she starts throwing her stuff into one of the washers just as the light flickers and one of the dryers stops. She starts the washer and turns around just as a dryer door swings open. Suddenly, something starts throwing the clothes in that dryer out as a stunned Isabel watches. Slowly, she goes to see what could be throwing the stuff out when suddenly one of the gray people starts crawling out of the dryer. Isabel ducks back and tries to hide, but is found and absorbed by the gray person. Later, we see Isabel arrive back home and call out for an absent Isabel. She goes to her computer and finds that infamous message. She clicks on it and sees Tim staring out at her. Her cell phone rings and she hears Tim saying on it that he sees her, although his mouth on the monitor isn't moving. She shuts the monitor and phone off and ducks into Isabel's room, but the monitor there is on and her phone rings once again, where Tim continues to tell Mattie that he sees her. She hangs up and calls Isabel's phone, which goes off on the vanity next to Mattie. She hangs up and wakes Isabel, who is lying in her bed and covered in black marks. Mattie gets her out of bed and puts a blanket around her, and Isabel starts saying that They are coming for everyone, even Mattie, and that there's no way to hide from them. Mattie asks what they want, and Isabel says, "They want what they don't have anymore...they want life." Mattie gets up and goes to call 911, but just gets a busy signal. She looks back at Isabel just in time for Isabel to disintegrate into nothingness. Mattie screams and quickly calls Dexter, who has just found a possible cure for the virus making all this happen taped underneath Josh's computer. He avoids a gray person that is trying to absorb him and answers Mattie's call, saying that he'll pick her up in front of her dorm.
Ten minutes later, we see Mattie nervously waiting outside for Dexter. He pulls up and she gets in his car, explaining what happened. He tells her that he thinks he found Ziegler and a way to stop this, and she takes this as good news -- until a car doing no less than seventy hits them on the side. The pair get out of the car and run for the building Ziegler is supposedly at. On the way, they encounter a family who basically gives them a five second recap of everything they already knew and cautions them to stay out of cities, since they can come through anything electronic. Dexter and Mattie start running again and eventually come to the computer company where Ziegler supposedly is. They find his office (ducking a few grays along the way) and break in, only to have him break out of a closet and immediately seal the door shut with red tape. He tells them who he is and that they found bandwidths that they didn't even know existed, thus opening the door for the gray people to come through from the world of the dead, and that for some reason they are only stopped by red tape because it's too high a bandwidth for them to break through. After some "convincing" by Dexter (re: threatening), Ziegler tells them that the best place to put their cure is in the main central hub in the basement, although he doubts it would work. They ignore him and run for the elevators down to the basement, but on the way some gray people get between them, keeping Dexter from getting on the elevator. The doors close and after a few bumps, Mattie gets to the bottom floor. She makes it all the way to the main hub and almost gets to the computer, but one of the gray people breaks through and starts trying to absorb her. Fortunately, Dexter interrupts them and pulls Mattie out of there (guess they were more interested in stopping the threat to their being than eating him). She tells him that it's too late and the cure won't work, but he ignores her, grabs the card, and heads back in. He starts uploading the cure and manages to crash the system, but suddenly everything starts rebooting, meaning the cure didn't work. He hightails it back to Mattie and the two run out of there. Outside, they look back and see a shitload of gray people on the roof of the building just before a jet crashes into it, utterly destroying everything inside. The pair find a pickup truck with keys still in it, and with half a tank of gas, drive out of the city. Mattie asks Dexter how far he thinks the half-tank will get them, and he says, "We'll find out."
Much later that night, we see the truck containing Dexter and Mattie by the side of the road. As the two are waking up, we hear the radio saying that there are survivors and that the signal containing the gray people can be transmitted through any PDA, pager, walkie-talkie, or cell phone. Mattie and Dexter sit upright and look at Mattie's cell phone on the dashboard with it's one-hundred percent transmission read and then look outside just in time to get a window smashed open by one of the greys. Suddenly greys are trying to get in all over the car, and Dexter floors it, hoping to throw them off. After a tense few minutes, the greys lose any strength they had and just fall off into the distance. Dexter asks what happened and they both see that Mattie's cell phone has lost its signal. Quickly Mattie throws the phone out the window and as the pair ride into the sunrise and come upon an encampment of survivors, Mattie reflects on how what had been intended to bring humanity together -- cell phones and the internet -- ended up destroying humanity and how although the cities now belong to the greys, basic humanity is still alive in the dead zones, and as we hear Mattie say this, we head back into the city and see Josh staring out at the remains of the city, burning and uninhabited by humanity.