The team must treat an agoraphobic who refuses to leave his house, and have to work around Cuddy, who is less than thrilled at having hospital equipment relocated. Meanwhile, House is plagued by an itch, and Cameron and Chase have relationship issues.
When House and Wilson disappear off the grid for several days, without explanation, the team is left to deal with a difficult case concerning a 6-year old with numerous problems and complications, including an overbearing mother who also happens to be her physician.
Wilson arranges for House to make a deal with Tritter, but House refuses. Meanwhile, Cuddy cuts House off Vicodin and removes him from the team’s case: a 15-year-old little person who entered the hospital with a collapsed lung and anemia.
While trying to figure out why a young patient won’t stop bleeding, House takes Cuddy’s challenge and goes off Vicodin for a week in exchange for no clinic duty for a month. If House and his team can’t determine the source of his patient’s blood loss, the 16-year-old car accident victim will die in a matter of days. As House’s withdrawal symptoms become more and more severe, his directives for his patient are more harsh and risky than usual, forcing Foreman and Cameron to fear he may not be thinking clearly enough to save the patient’s life.
House and Park treat a patient, Benjamin, who collapsed after making a surprisingly large charity donation, and come to suspect that the altruistic behavior is a symptom of a deeper disorder. When the patient offers to donate an organ for another patient, the doctors must convince Dr. Adams to help them confirm whether Benjamin is in his right mind or not.
While Foreman takes on a pediatric case on his own, the rest of the team deals with a 16-year-old factory manager and emancipated minor who collapses at work. When Foreman’s patient takes a turn for the worse, he’s forced to question whether he can deal with the situation on his own, or if he needs House’s help.
After saving a stranger who fell onto subway tracks, a man suddenly collapses despite appearing to be unscathed; House tries to avoid a dinner with Cuddy and her opinionated mother.
House and the team take on the case of a young boy who has violent dreams of being choked, and then wakes up but still can’t take in air. Meanwhile, Park is having intimate dreams involving co-workers, which causes the team to question whether or not there’s significance to what each of them dreams. Dominika discovers House has been keeping a secret from her and Wilson drops a bombshell on him.
As House and his team are working on the diagnosis of a man with a giant, swollen tongue, the husband of a former patient walks into House’s office and shoots him. House continues to treat his patient from his ICU hospital bed with the shooter, who has been shot by hospital security and hand-cuffed to his bed, as his roommate. When the after-effects of the shooting begin to impact House, he starts to question his own ability to diagnose properly. As his patient’s body deteriorates, House struggles through his self-doubt and must trust his team to find a way to solve the case.
House and the team take on the case of Sir William, a "knight" in a closed-off community of men and women living according to the ideals of the High Renaissance. As the team searches the medieval village for environmental factors contributing to Sir William's rapidly deteriorating health, Thirteen and Sir William debate the acts that define honor and loyalty, especially in regard to the "queen" of the community, one of Sir William's most frequent visitors. Meanwhile, Wilson starts over with an ex.
A homeless man with a history of drug abuse is admitted to Princeton Plainsboro with burns and scars on his chest. Meanwhile, Cuddy reveals her guilt to Wilson about breaking up with House.
On the eve of Thanksgiving, House and the team take on the case of James Sidas, an exceptionally brilliant physicist and author who traded his successful career for a job as a courier. For the ailing patient, intelligence is a miserable burden that has prompted depression and addiction, and this, coupled with a myriad of strange symptoms, nearly stumps the team. Meanwhile the doctors at Princeton Plainsboro wrestle with strained personal relationships.
Facing a 6-month jail term, and the realization that he won’t be there for Wilson at the end, House finds himself examining his entire life while contemplating a dismal future without his best friend.
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.
The Cylons learn that the Final Five are in the Colonial fleet. Some of the Cylons want the Cavil model to stop lobotomizing the Raider ships. Starbuck desperately tries to convince the others that the fleet is going the wrong way in their search for Earth.
With Adama out of action, Colonel Tigh takes his position as commander of the Galactica. Boomer is in jail, and the cat’s out of the bag – she’s a Cylon.
As Sam Anders recovers from his head injury onboard the Galactica, he begins to remember events from ancient Earth. The Final Cylon struggles with the fallout from the Final Five’s former plans. One of the humanoid Cylons vows to get revenge for being created in the image of Man. Tyrol informs Admiral Adama about the extensive structural damage on the Galactica.
Apollo formulates a plan that threatens the very existence of the Cylon culture. Adama and Roslin must decide whether to follow through on the plan to use a biological weapon against the Cylons. D’Anna Biers (Number Three) believes Baltar knows who created the virus that infected and disabled the Cylon baseship. She is willing to take extreme measures to learn the truth.
The Sagittarons allege that a doctor is discriminating against them. As Helo investigates, he becomes concerned that the doctor may even be murdering patients. Meanwhile, Athena unwittingly brings Hera to the doctor for treatment.
The fleet has found a source of water, but who will take on the difficult and dangerous job of mining it from the icy planet? Commander Adama and President Roslin send Lee to the Astral Queen, a prisoner transport ship, with an offer for its inmates: Volunteer for this mission and earn “freedom points”.
