The story takes place in Hollywood, and revolves around Dr. Henry Carter (Spacey). Most of Carter's patients are luminaries in the film industry, each undergoing their own life crises. Carter lives in a large, luxurious house overlooking the Hollywood Hills, and has published a hugely successful self-help book. However, Carter is disheveled, and he is frequently seen alone in his large house. He smokes marijuana at home, in his car, and behind his office when not seeing patients. Carter routinely drinks himself to sleep around his house, waking up in his clothes. He never enters his bedroom. Later in the movie, it is revealed that Carter's wife has recently committed suicide.

Despite his own problems, Carter remains attentive to his patients, maintaining his incisiveness, compassion, and strong doctor-patient relationships. It is never stated whether Carter is a psychiatrist or a psychotherapist; however his sessions with patients consist of deeply involved talk therapy. He is not shown prescribing medication.

Much of the ensemble cast comprises Carter's patients. Patrick is a high-powered talent agent who is both narcissistic and deeply idiosyncratic. Shamus (Jack Huston) is an actor addicted to cocaine, and one of Patrick's biggest clients. Jack (Robin Williams) is a popular celebrity, and works with Shamus. Kate (Saffron Burrows) is an actress in her thirties, and another of Patrick's clients. She is intelligent, compassionate, and poised, but is facing fewer career opportunities because of Patrick's notion that her age is a limitation. Her rock-star husband is neglecting her and cheating on her.

Carter's newest patient is Jemma (Keke Palmer), a troubled high-school student. Jemma has been referred to Carter by concerned school officials, and Carter takes her case pro-bono. Jemma is an avid moviegoer, who aspires to become a filmmaker. Like Carter's wife, Jemma's mother committed suicide.

Carter has few friends. He spends time with Jesus, his quirky pot dealer (Jesse Plemons). Carter also socializes with Jeremy (Mark Webber). Jeremy and Carter are loosely related through Carter's deceased wife. Jeremy is a struggling young screenwriter. He finds romantic interest in Patrick's assistant Daisy (Pell James). Jeremy also derives creative inspiration from Jemma.

Jeremy secretly steals Jemma's private file from Carter's office. He pursues a platonic interest in Jemma. He writes his breakthrough screenplay about Jemma, and, with Daisy's help, Jeremy succeeds in gaining Patrick's interest in the screenplay.

Jemma discovers the screenplay, and feels betrayed by Jeremy, and Carter angrily attacks Jeremy for his deception. However, Carter accepts his own professional responsibility in the situation, which he unknowingly allowed. Carter must stop treating Jemma, though he had just begun helping Jemma finally come to terms with her mother's suicide.

Carter suffers a breakdown on a live television talk show, alarming the host (Gore Vidal) and the viewers when he states publicly for the first time that his wife committed suicide. He denounces his book as "bullshit" and himself as a fraud, and storms off of the set. Jemma, Daisy, and Jeremy are seen reacting to Carter's on-air outburst.

Later, Carter and Jeremy are mysteriously invited to a meeting at Patrick's office. Patrick seats them in a conference room, where Jemma is already waiting. To their surprise, Jemma exclaims her affinity for Jeremy's screenplay. Patrick announces that he will be representing Jemma and making Jeremy's screenplay into a movie.

Carter, having disposed of his drug supply, approaches Kate at home. He tells her he doesn't want to see her anymore "...professionally", indicating his interest in seeing her romantically. She smiles.

Later, at night, Carter enters his bedroom, wearing pajamas. He momentarily regards his (former) marital bed, before climbing into it and turning off the light.