House and the team take the case of Sir William, a knight from a 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. Meanwhile, Wilson starts dating his ex-wife, Sam.

The team takes on the case of an ailing groom-to-be who harbors undisclosed secrets from a previous relationship. As his fiancée tries to get answers to her many questions, a frustrated team winnows down the possibilities. Meanwhile, House spends extra-curricular time with his Princeton Plainsboro colleagues at Wilson's insistence, performing a karaoke rendition of a Gladys Knight & The Pips classic with Foreman and Chase during a raucous night out.