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The film opens up in the early morning. A man is cycling by as a paper boy is driving around delivering newspapers. A newspaper hits a door and the main article’s title is “Life Has A Mind” by Steve Lopez (Robert Downey Jr.).  Steve Lopez is cycling around town and goes in the opposite direction of a bunch of cyclists. Lopez gives an internal monologue chronicling a biking accident which occurred near a construction site. His bike hits a bump and he hits his head badly on the pavement. In the next scene he’s in an ambulance being driven to a busy hospital. While in the emergency room, Lopez writes down his thoughts as if writing an article. He is given an MRI and after being cleared, takes a taxi home.  He checks his messages (there are none), continues to narrate into a tape recorder.

The next morning, he goes into work at the L.A. Times. He continues to talk to himself as he walks through the halls about how much he hates hospitals and health care under the governor. The Editor of the L.A. Times, Mary (Catherine Keener), walks down the cubicles past Steve as he is greeted by the people in the neighboring cubicles. Steve and Mary banter about an article Steve was supposed to write before his accident but he tells her that he won’t write it as she goes off to her office.

Steve is then sitting outside on the boardwalk drinking a soda. He hears a violin playing and starts to walk around the plaza until he finds the sources. He finds Nathaniel Ayers (Jamie Foxx), playing a two string violin under a statue. Steve immediately realizes that Ayers is a schizophrenic and tries to walk away but Ayers follows him for a bit until Steve introduces himself. Ayers tells Steve that he once went to Julliard.

Steve is in his office making a call to the Registrar’s office at Julliard when Mary sits down next to him. She tells him that the LA times stock situation is looking pretty dire before switching the conversation over to their son. Mary tells Steve to call him but Steve says that whenever he calls their son won’t call him back. He sends her away stating that he is trying to find a story before deadline. The Registrar’s office tells Steve that there is no record of a Nathaniel Ayers ever attending Julliard and then hangs up on Steve. He says he’s “not taking the blood story” but as he crosses “violinist” off his list of potential stories it’s clear he’s out of options. He is then seen sitting in front of a young nurse preparing to draw blood from him. As part of his blood test, he goes to urinate in a cup. While he’s peeing he drops the cup and slips when he gets a callback from Julliard. The Secretary tells Steve that she only checked the graduates but when she checked all students, she found that Nathaniel Ayers dropped out of Julliard during his second year.

That night, Steve returns to where he met Nathaniel and narrates the content of the article “Points West” detailing how Nathaniel is missing while calling him “shy.” Steve drives back to his apartment and finds that raccoons ruined his lawn. His neighbor tells him that coyote urine will keep the raccoons away. Steve spends the night walking around his messy apartment while listening to music. The next morning, Steve is calling the head of the coyote urine business when he sees Nathaniel on the side of a busy intersection. He stops his car and says hi. Nathaniel turns away from him and doesn’t speak. Steve waits patiently against the intersection wall for Nathaniel to finish up. Nathaniel plays the same group of notes over and over until he can’t do it anymore. Steve tells Nathaniel that he wants to write a piece about him and how he ended up on the street. Steve asks him about his family, but Nathaniel can’t focus and give direct answers.

Steve calls Nathaniel’s sister to learn more about him. A flashback shows a young Nathaniel walking down the street carrying a cello. He met with his music teacher and went on and on about how much he admired Beethoven’s work. He played the cello for his teacher and the teacher thought that he was an incredibly gifted student. Instead of playing sports, his sister said that all Nathaniel would do was play the Cello. Nathaniel’s mother told him that when she listened to him play, she heard the voice of God. Steve writes an article detailing what he learned from Nathaniel’s sister. After it is published, an old lady reads it and sends Steve her old Cello with the request that he give it to Nathaniel with her prayers. As Steve is driving, he almost hits Nathaniel and gets him to walk over to the side. Steve is concerned about Nathaniel’s safety and the Cello and arranges for Nathaniel to keep the Cello in a music store with the permission of the owner. Steve let’s Nathaniel play the instrument on the street for a “test run.” Nathaniel plays for Steve and Steve is visibly moved by the piece. Steve drives away with the Cello to put it into holding.

He passes through a bad neighborhood where a bunch of homeless people are gathered on the sidewalk next to the mental health clinic. He pulls up to the gate and asks to speak to someone named David. He and David put the Cello in storage and then Steve sticks around to wait for Nathaniel. He sees all the people with their problems and seems a bit troubled. He goes outside and continues to wait for Nathaniel. He mingles with several homeless people. He waits until nightfall and then goes home. He starts to put coyote urine throughout his lawn when a bag explodes on him.

The next morning Steve is seen interviewing a worker on the side of the work about a religion which has no beliefs. Steve gets a phone call and hears Nathaniel playing the Cello. He goes back to the storage unit of the mental health clinic and sees Nathaniel playing for the people gathered around.

Another flashback shows Nathaniel in his first apartment and subsequent performances at Julliard. At one point he is surrounded by people and in the next he is in an empty auditorium. He calls his mother and shares the fact that he can’t always tell what is going on in the world around him and that he can’t differentiate what’s real and what’s not. His musical performances grow more erratic and his paranoia starts to set in as a voice says “they can hear your thoughts Nathaniel.” He runs out of the auditorium and runs away because the voices tell him to. He hides in a closet and lets the voices overwhelm him. 

Steve asks David if he will diagnose Nathanial’s problem. David says that it would be pointless. Steve asks if there’s a medication that can help Nathaniel but David tells him that the last thing he needs is another person telling him he needs medication. Steve goes to find Nathaniel but Nathaniel is gone. Steve goes out to his car and just sits there, observing the interactions of the people outside before going to find Nathaniel. He walks past some drug users and down the street before seeing the police around a dead body. As he looks down to see the person, he sees Nathaniel next to him. Nathaniel finds a place to sleep and starts cleaning the area a little with a broom before setting up his bed. He tells Steve that he will end up like Beethoven and lie down and die. Steve spends the night with Nathaniel on the street and they talk. Steve tells Nathaniel that it is no place for him to live, but Nathaniel is adamant that this is where he should be.

The next morning, Nathaniel and Steve are having lunch in front of the L.A. Time Building. Steve offers to bring Nathaniel to see an Orchestra perform Beethoven. Steve tries to get Nathaniel to leave the health clinic and the garbage but loses his temper with Nathaniel. He apologizes. They move Nathaniel’s cart and bring it with them to the orchestra. Nathaniel watches the orchestra with Steve and as they perform, Nathaniel focuses only on the music and imagines himself alone and then imagines each sound striking up a color.

Later on, Steve and Mary are at a karaoke bar with their coworkers and Steve is telling her about Nathaniel’s enjoyment of the music and the grace Nathaniel gets listening to music. Steve finds Nathaniel’s love of music to be awe inspiring. He upsets Mary when he tells her the he has never loved anything like Nathaniel loves music. He tries to recover from that but Mary leaves and tells him the Mayor wants to talk to him. The Mayor announces that he intends to add 50 million dollars in aid to the city’s homeless community.

Nathaniel visits Steve at the office. Steve is busy and tells Nathaniel he can’t perform in front of the building, so Nathaniel waits on the other side of the building. He calls Graham Clayton (Tom Hollander), a cellist, to rehabilitate Nathaniel. Steve convinces David to help find Nathaniel an apartment where Nathaniel can live and rehabilitation. Nathaniel doesn’t want to live in an apartment. He frustrates Steve but then starts to question Steve about his family. Steve was once married to Mary, but they divorced. Their son, Tom, is in college and won’t talk to Steve. Steve tells Nathaniel that if he doesn’t go to the apartment, he will be on his own. 

Another flashback details Nathaniel’s mental breakdown in his old apartment. He is slowly driven insane by the voices until he cries on the floor of the apartment. A week later, Steve and Nathaniel move Nathaniel into the place where he will live and practice. It is a small apartment with a bed and a bathroom. There is enough room for Nathaniel to be comfortable and practice, but Nathaniel is afraid to enter the room. Steve patiently tells Nathaniel that he can do it. Eventually, Nathaniel enters the room with his stuff. Nathaniel doesn’t like the room because it doesn’t have the natural sounds of the city and reminds him of the night he spent going insane.

Steve introduces Graham and Nathaniel. Graham brings Nathaniel the sheet music for Bach to begin Nathaniel’s rehabilitation. Graham is impressed by Nathaniel’s skill but notices that it needs to be refined. Graham tells Nathaniel that God gave Nathaniel a gift and that Nathaniel shouldn’t waste it. Nathaniel gets upset with Graham and declares that Steve is his God. Steve gets frustrated with David because Nathaniel is attached to Steve and Steve doesn’t want to fail Nathaniel. Steve asks David to help Nathaniel with psychiatry and medication. Steve tells David that if he puts Nathaniel into forced rehab for two weeks, that might be enough to get Nathaniel straightened out.

Steve goes to an award show which honors Steve’s achievement in bringing Nathaniel’s story to focus. Nathaniel calls Steve and tells him all the things he needs from Steve. Steve hands the phone off to Mary, and she listens to all the things Nathaniel says. She gets drunk and tells Steve that he’s good at avoiding responsibility. Steve calls her a drunk and tells her she needs someone to drive her home.

Graham calls Steve the next day and tells Steve that Nathaniel should have a recital. Graham tries to pray with Nathaniel before the recital. Nathaniel wheels out his card and takes his cello before sitting down in front of the audience. As Nathaniel starts to play, he begins to have a psychotic episode and hear the voices. He experiences a flashback to when his mother was taking care of him. She tries to feed him, but Nathaniel instead takes the spoon and starts feeding her instead. Graham puts his hand on Nathaniel to bring him back to reality, but Nathaniel freaks out and runs away. Steve picks up Nathaniel’s Cello and looks for Nathaniel with his car. Nathaniel flashes back to when he left home. After the freak out, he ran away with his mother asking him where he would sleep.

As Steve searches for Nathaniel, he sees the police launching a large scale arrest of the homeless and drug users. Steve finds police guarding a bloody shirt and is told that a bunch of kids with baseball bats beat a man brutally. Steve goes to find him and checks every hospital in the area looking for Nathaniel. He spends all night looking for him. The next morning, Steve gets a call from David telling him that Nathaniel is at the clinic eating breakfast and that he spent the night in the apartment. Steve visits Nathaniel at his apartment and returns his cello. Steve gives Nathaniel a mini-bust of Beethoven and asks him if he did a good job. Jennifer, Nathaniel’s sister, is ready to take over as Nathaniel’s caretaker. Steve leaves him the forms and tells him to read them before he signs them.

Nathanial reads the forms and throws them away when he realizes that it’s about his schizophrenic state of mind. Nathaniel gets violent with Steve and tells Steve that if he sees him again he’ll gut him like a fish. Steve runs out of the apartment the minute he gets free and leaves Nathaniel to the voices.

A little while later, Steve is taking shots in a bar. He visits Mary at her house. They reminisce about when they moved into the house with Tom. Steve comes to grip with his failures as a father and a husband. He apologizes to Mary and tells her that he thought he was helping someone with a gift who had lost their way. He tells her about what happened with Nathaniel and how he doesn’t know how to fix it. He tells her that he officially resigns from everything since he can’t get it right. Mary tells him that Steve would never have been able to cure Nathaniel and that all Steve could do was be his friend.

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Jennifer flies into L.A. to get her brother.  Steve drives her to the clinic and she goes in to see her brother. The clinic is not as crowded as it was before the cops arrested people. Jennifer sees Nathaniel sitting and slowly approaches him. They sit together for a while as Steve watches from the car. Nathaniel remembers that Jennifer is his sister and she holds his hand in comfort. Steve sits outside dangling his car keys until the pair comes out. Nathaniel looks down at Steve and apologizes for threatening Steve. Steve tells Nathaniel that it’s ok. “Mr. Ayers, I’m honored to be your friend.”

Steve begins his narrative epilogue as Mary, Steve, Jennifer and Nathaniel watch the orchestra performs. A year ago, he met Nathaniel and thought that he could help him. His mental state and well being haven’t changed but he no longer lives on the street. Psychiatrists tell Steve that his friendship gives Nathaniel balance, but he can’t attest to it. Steve tells himself that Nathaniel’s friendship and courage has made him a better person. They watch the orchestra perform in silence.

An after credit card tells the audience the following: Mr. Ayers still sleeps inside and is a member of LAMP. He continues to play the cello, as well as violin, bass, piano, guitar, trumpet, French horn, drums and harmonica. Mr. Lopez continues to write his column for the L.A. Times. He is learning to play the guitar. There are 90,000 homeless people on the streets of Greater Los Angelos.

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