House awakens in the Mayfield Psychiatric Hospital after suffering through the painful effects of Vicodin withdrawal. Feeling better, he wants to leave. Dr. Nolan refuses to sign a recommendation to the board of medicine saying he is able to return to work. House resigns himself to stay at the hospital and get his clearance.

House tells Dr. Beasley that he will do anything to get that recommendation. He even threatens to turn Ward 6 upside down if he has to. House meets his new roommate Alvie, a manic-depressive who is manic while off his medication. House then begrudgingly participates in group therapy with Dr. Beasley. House tries to get kicked out by humiliating everyone during a basketball game in the yard, but the doctors won't stand for his antics.

House meets a woman named Lydia who plays piano for her sister-in-law, an unresponsive patient on the ward who was a musician. He is intrigued by Lydia.

After House is put in solitary confinement, he comes up with a new strategy to try to get kicked out. He addresses the group in therapy to apologize for his insults, but really goads them into creating havoc on the ward over table tennis.

From the hospital window, House sees Dr. Nolan get into a car with a woman. House convinces Alvie to break into Nolan's office to get the scoop on him. Alvie is unsuccessful, so House comes up with another solution. He pretends to beat up Alvie in the rec room. House is put on Haldol, but he pockets the pills in his cheek and give them to another patient in return for the man's phone privileges. House calls Wilson and asks him for help blackmailing Nolan. Wilson refuses, saying that Nolan already contacted him to warn that House may try to do something like this.

A therapist named Dr. Medina makes House undergo a drug test to prove he is taking his meds. Since he is pocketing all his pills, House gets the patient with all the Haldol to submit his urine instead.

House starts to adjust to life inside the institution. His only respite is Lydia's regular visits. They discuss music therapy, and Lydia agrees to bring the cello that her silent sister-in-law used to play.

A new patient named Steve thinks he is a superhero who goes by the moniker "Freedom Master." Medina provokes him to break his delusion about his dead wife, but Steve has an episode and is drugged into a catatonic state. House gets angry at Medina over this and turns to Nolan. Dr. Nolan admits that he had switched House to a placebo instead of the Haldol because he knew he was pretending to get better.

House confesses to Alvie that he is out of plans. House waits for Lydia to bring the cello, and he has Steve help her at her car. Lydia willingly gives her car to House for him to kidnap the depressed Steve. House takes him to a carnival where they are lifted in a wind tunnel ride as if they were really flying. Steve is overjoyed, but then really believes he can fly because he's under the impression that he's a superhero. He jumps off the roof of a parking garage.

With Steve badly injured, Dr. Nolan wants House to leave the institution because he is a distraction to the group. House earnestly asks for help in getting better. He begins therapy with Nolan and takes his medications, much to the chagrin of Alvie, who feels betrayed.

Nolan brings House a suit and has him mingle at the hospital's fundraising party. His assignment is to make connections with strangers. It is painful for House at first, but then he has fun toying with people. Lydia becomes his accomplice. As she leaves, she gives House a kiss.

House is eager to discuss the kiss with Nolan. Lydia is married. He also feels guilty about what happened to Steve, and Nolan tells him to apologize personally. During group therapy, Dr. Beasley suggests the patients put on a Ward 6 talent show. House has an idea of how to help Steve, who had been trying to "save" the silent girl with a music box hidden in the nurse's station. He called it her "voice". House convinces Beasley to allow them to get the music box, but Dr. Nolan comes in to break up the group and wheels Steve away, as House's plan failed.

House rebuffs Lydia because he knows that, in the end, someone will get hurt. House is given a day pass by Dr. Nolan who requests his presence. He arrives at a hospital to find Nolan at the bedside of his dying father. A tearful Nolan asks House for a consultation. Although House has nothing to add to the diagnosis, he accuses Nolan of having no one else to turn to but his own patient. Dr. Nolan tells House to leave but he stays sitting with the Doctor in silence.

When House returns to Mayfield, he finds Lydia upset over her sister-in-law. He apologizes for pushing her away. With both of them in pain, they turn to each other for intimacy and they succumb to a night of passion.

The residents hold a talent show. House doesn't participate at first, but he is coaxed into helping Alvie when he can't continue with his rap on stage. House apologizes to Steve, and as he wheels him away, Steve breaks from his silence and gives the silent woman the music box he was holding. For the first time, she speaks to say thank you. It is a healing moment. House is proud of himself, as it was he that realised that Steve and the music box were the key to curing her. Lydia arrives and House takes her in to see the group watching the no longer silent girl playing the cello.

Dr. Nolan tells House that Lydia is taking her sister-in-law to a rehab facility in Arizona with Lydia's husband. House gets an overnight pass and goes to see Lydia at her home. He is startled when Lydia's young son answers the door. House wants her to stay, and Lydia says she wants to but ends up asking House to leave. Later, House talks to Dr. Nolan about his feelings, who is now convinced that House deserves the recommendation to the medical board.

House is discharged and gets on a bus back to Princeton. The bus sports an advertisement for a skills improvement institute saying "Prepare to Succeed". After the departure of House, Alvie decides he wants to get better and goes back on his medication. The last shot is of House wearing Alvie's shirt, sitting in the back of the bus with the hospital receding in the background.