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 situation to her own.
House copes with a patient whose symptoms conceal a greater problem, but spends much of his time dodging Cuddy's orders to give performance reviews, and fighting with Amber over who gets to spend more time with Wilson.
House is convinced one of the actors on his favorite soap opera “Prescription Passion” has a serious medical condition after observing his symptoms on television. House decides to intervene and take matters into his own hands, but both the actor and House's own team dismiss House’s assessment and do not believe there is anything wrong with him.
Under Cuddy’s pressure to choose his team, House gives the candidates a case of a former punk rock star who is a drug user. Whoever diagnoses the patient is going to have a future as a member of House’s team.
A mother's sudden paralysis during a indoor rock-climbing incident leaves her daughter injured, and House's new team looking for a cure. Meanwhile, House organizes his new recruits' Secret Santa gift exchange... with a few twists of his own.
Based on practically no information and no medical history about a mystery patient sent by the CIA, House is using some unorthodox methods to diagnose and treat him. Meanwhile the remaining candidates are questioning Foreman's judgment.