A gun-wielding man from the waiting room at the Princeton-Plainsboro clinic takes House, Thirteen and several patients from the waiting room hostage in Cuddy's office. The man claims to be sick with a long undiagnosed illness and demands medical attention from the best doctor in the hospital, threatening to kill any hostages necessary along the way.

During a day in the life of Princeton Plainsboro's Dean of Medicine, Dr. Lisa Cuddy, the inner workings of the hospital are seen through her eyes. This day proves to be especially trying as Cuddy wrestles with myriad hospital issues and staff disputes that test her perseverance and skills as an administrator, all while juggling issues in her personal life.

It’s election season, and in the midst of a tight campaign, an incumbent New Jersey senator’s campaign manager falls ill with liver failure and temporary paralysis. Cuddy pushes House to add a female doctor to his team by hiring brilliant third-year medical student Martha Masters in Thirteen’s absence.

House participates in a school’s Career Day and breaks a few rules by sharing explicit medical stories. Waiting outside the principal’s office, he meets two fifth-grade students who assess House’s relationship woes and try to help him understand how his selfish antics get in the way of showing Cuddy how he really feels.

A prosecutor suffers from what he believes to be cardiac arrest during an interrogation at the witness stand. The team's preliminary diagnosis is hyper-anxiety, but when Adams and Park investigate the patient's home and find a hidden arsenal of firearms, they uncover a more alarming and deep-seated psychological disorder.

House and his team treat an Alzheimer's patient who vomits blood and flies into violent rages. Meanwhile, when Wilson tells House about a patient who has never had sex with her husband of 10 years, claiming A-sexuality, House makes a wager with him that there has to be an underlying cause.