Smithers is placed in charge of the power plant after Mr. Burns is thrown in jail for possession of stolen artwork. But the plant employees work together to get Mr. Burns out of jail when Smithers abuses his powers as boss.

When Chuck can choose between the best agents for an undercover mission, he has only Sarah on his mind, so he and his friends team up to win her back.

Chuck's fate as a spy rest on a single mission. Chuck learns that his latest solo mission will be a final test to see if he is ready to be a spy. Chuck needs to put everything he has learned into action to avoid going back to his old life while Sarah and Shaw observe his every move.

Charlie runs into Chelsea's old friend Gail again. Alan gets a new female patient at his chiropractic office.

Joining J.D. at Sacred Heart Hospital are fellow residents Chris Turk - J.D.'s college buddy who is part of the more elite surgical group, and the beautiful but socially awkward Elliot Reid. Keeping a watchful eye over these young doctors are the caustic chief of medicine, Dr. Bob Kelso; the abrasive but caring Dr. Perry Cox; and no-nonsense nurse Carla Espinosa. Neil Flynn also portrays J.D.'s nemesis, the hospital janitor, who never seems to miss an opportunity to harass his target.

House and team tries to diagnose a high school senior suffering from blackouts and hallucinations, and are forced to take a controversial approach. Meanwhile, Wilson attempts to furnish his new condo, and Taub brings his personal life into the workplace.

In the aftermath of personal tragedy, Wilson resigns from the hospital... and from his friendship with House. Meanwhile, Thirteen struggles with her personal medical problems while helping treat an executive assistant with a similar personality to her own.

With his diagnostic team gone, House tries to diagnose a young woman who survived an office building collapse. With the condition getting worse, Cuddy puts pressure on House to hire a new team, but instead attempts a differential diagnosis with help from the janitor.

After recovering from his gunshot wounds, House works feverishly on two cases at the same time: a paralyzed man who drove his wheelchair into a swimming pool and a woman who became paralyzed after a yoga session.

A death row inmate is felled by an unknown disease and House decides to take on the case, over Cuddy and Foreman's objections. House also has to deal with Stacy who is working closely with him, while Cameron has to cope with a dying patient.