Dr. Gregory House (Hugh Laurie) – Department Head: Diagnostic Medicine. Dr. Gregory House is a rebellious diagnostician with a double specialty in infectious disease and nephrology. Dr. House utterly lacks a bedside manner and prefers to avoid direct contact with his patients however possible. Due to an infarction in his right thigh, House lost a substantial portion of the muscle in his upper leg and must use a cane to assist with walking (although, where most would hold the cane in the hand opposite the injured leg, House holds the cane on the same side as his injury). As a result, House is also forced to deal with constant physical pain, which he manages through a dependency on the prescription pain medication Vicodin. Although his behavior can border on antisocial, misanthropic or sociopathic, House is viewed as a genius physician whose unconventional thinking and excellent instincts have afforded him a great deal of respect and an unusual level of tolerance from his colleagues and the medical world. House is eventually replaced by Chase after he fakes his death in the series finale, "Everybody Dies."
Dr. Lisa Cuddy (Lisa Edelstein) – Administration: Dean of Medicine, endocrinologist. Dr. Cuddy attended the University of Michigan for graduate studies, where she first met Gregory House. She has the distinction of being one of the few characters on the show (Dr. Wilson being the other) who can match wits with the silver-tongued Dr. House in conversation (and arguments) and be considered one of his "friends". She often is left to pick up the pieces of House's questionable medical practices. She is also one of the few people who can stand House's hostile manner, strange requests, and his many crude (sometimes nosy) habits. Although she frequently criticizes House's methods, she does trust his decisions to be in the best interest of his patients. Over the course of the show, it is seen that she is one of the few, if not only, people who would hire House at all, due to widespread disapproval of House's results-oriented methods and constant insubordination. A developing arc in season five indicates that she has (and may have always had) very strong feelings for House; in season five's "Saviors" she refuses to answer when asked if she is in love with House, dismissing it as "a ridiculous question." House has described her as a second rate doctor. In season seven, Cuddy and House start dating but she eventually breaks up with him when he starts using Vicodin again during her health scare. She leaves the hospital after House drives his car into her house and she is replaced by Dr. Foreman in the beginning of Season 8.
Dr. James Wilson (Robert Sean Leonard) – Department Head: Oncology. Dr. Wilson is House's best friend. Wilson is very popular and well-respected by both his colleagues and his patients, making his close friendship with the anti-social House especially puzzling to the other hospital employees. Wilson claims that his job and his "stupid, screwed up friendship" with House are the two most important things to him. He, along with Cuddy, usually finds himself aiding and abetting House's Vicodin addiction and his very eccentric methods. In Season 8, Wilson is diagnosed with cancer. Wilson is said to have 5 months to live. Wilson is one of the few people to know that House faked his death and, along with House, quits his job as a doctor.