In 2005, Steve Lopez (Robert Downey, Jr.) is a journalist working for the L.A. Times. He is divorced and now works for his ex-wife, Mary (Catherine Keener), an editor. A biking accident lands Lopez in a hospital.

One day, he hears a violin being played beautifully. Investigating, he encounters Nathaniel Ayers (Jamie Foxx), a homeless schizophrenic, who is playing a violin when Lopez introduces himself. During the conversation that follows, Lopez learns that Ayers once attended Juilliard.

Curious as to how a former student of such a prestigious school ended up on the streets, Lopez contacts Juilliard but learns that no record of Ayers graduating from it exists. Though at first figuring a schizophrenic who's talented with a violin isn't worth his time, Lopez soon realizes that he has no better story to write about. Luckily, he soon learns that Ayers did attend Juilliard, but dropped out after two years.

Finding Ayers the next day, Lopez says he wants to write about him. Ayers doesn't appear to be paying attention. Getting nowhere, Lopez finds and contacts Ayers' sister (Lisa Gay Hamilton), who gives the columnist the information he needs: Ayers was once a child prodigy with the cello, until he began displaying symptoms of schizophrenia at Juilliard. Unable to handle the voices, Ayers dropped out and ended up on the streets due to the delusion that his sister wanted to kill him. Without a cello, he has resorted to playing a two-string violin.

Lopez writes his article. One reader is so touched, she sends him a cello for Ayers. Lopez brings it to him and Ayers is shown to be just as proficient as with a violin. Unfortunately, his tendency to wander puts both Ayers and the cello in danger, so Lopez talks him into leaving it at a shelter, located in a neighborhood of homeless people. Ayers is later seen playing for the homeless.

A concerned Lopez tries to get a doctor he knows (Nelsan Ellis) to help. He also tries to talk Ayers into getting an apartment, but Ayers refuses. After seeing a reaction to music played at an opera house, Lopez persuades another friend, Graham (Tom Hollander), a cellist, to rehabilitate Ayers through music. The lessons go well, though Ayers is shown to be getting a little too attached to Lopez, much to the latter's annoyance. Lopez eventually talks Ayers into moving into an apartment by threatening to abandon him.

Lopez' article on Ayers gains so much fame, Ayers is given the chance to perform a recital. Sadly, he loses his temper, attacks Graham and leaves. This convinces Lopez' doctor friend to get Ayers help. But when Ayers learns what Lopez is up to, he throws Lopez out of his apartment and threatens to kill him.

While speaking with Mary, Lopez realizes that not only has he changed Ayers' life, Ayers has changed him. Determined to make amends, Lopez brings Ayers' sister to L.A. for a visit. Ayers and Lopez make up. Later, while all watch an orchestra, Lopez ponders how beneficial their friendship has been. Ayers still hears voices, but at least he no longer lives on the streets. In addition, Ayers has helped Lopez's relationship with his own family.

It is revealed in the end that Ayers is still a member of the LAMP Community, a Los Angeles-based nonprofit organization that seeks to help people living with severe mental illness, and that Lopez is learning how to play the guitar.