According to the episode title, it refers to a speech given by former U.S. Secretary of Defense Donald Rumsfeld on February 12th, 2002, about the lack of evidence of weapons of mass destruction in Iraq. The full quote is as follows: "Reports that say that something hasn't happened are always interesting to me, because as we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say, we know there are some things we do not know. But there are also unknown unknowns--the ones we don't know we don't know. And if one looks throughout the history of our country and other free countries, it is the latter category that tends to be the difficult ones."
Fox had a tribute to The Simpsons week, where shows on Fox mentioned or featured items from The Simpsons. In this episode, House refers to Cuddy's breasts as "Patty and Selma," referencing Marge's twin sisters from The Simpsons (1989), because "they're always smokin'."
Annabelle Attanasio, who guest starred as the patient, is the daughter of executive producers Paul Attanasio and Katie Jacobs.
At the 1980s dance party, Dr. House wears a 1780s suit and wig, a possible reference to Hugh Laurie's role as the Prince Regent in Blackadder the Third (1987).