At a renaissance festival, a knight fights for the "queen's" hand. He falls to the ground with red eyes but no wounds. Wilson dates his first ex-wife. House and Thirteen dress up to investigate at the renaissance festival.

A woman in an open marriage suddenly gets strong belly pain. Taub would like an open marriage. Wilson's new relationship with his ex is shaky.

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, performing a karaoke rendition of a Gladys Knight & The Pips classic with Foreman and Chase.

At therapy with Dr. Nolan, House tells about a cute amnesiac in ER, Wilson throwing him out and his old apartment being a mess after Alvarez broke in.

A famous novelist finishes her last novel and gets ready to shoot herself, when she has a seizure. House gives her a 72 hour psych hold to find out what's wrong with her. House and Wilson go on a go-kart double-date.

After a 200-year-old medicine jar found on an off-shore shipwreck shatters in a teenage girl's palm, she is admitted to Princeton Plainsboro for symptoms closely linked to smallpox. When the Center for Disease Control's Dr. Dave Broda institutes a lockdown on the hospital and suspends House's team's ability to diagnose, Masters is skeptical about Broda's diagnosis and becomes convinced that the patient is suffering from a different disease. The girl's father soon experiences similar symptoms, and House is forced to make a precarious decision that puts his own life in jeopardy. Meanwhile, Wilson and Sam comfort a 6-year-old chemotherapy patient who prompts them to examine their relationship.

Science and faith are called into question when a patient is admitted to the hospital following his reenactment of the Crucifixion. The patient, Ramon Silva, refuses to undergo the prescribed treatment, and the team learns that after his daughter's cancer was cured, he pledged an oath of self-sacrifice to God. With little time to save Ramon's life, the team struggles to understand his reasoning and seemingly extreme religious convictions, but eventually learn that faith is not an argument. Meanwhile, Taub questions his wife Rachel about her relationship with an infidelity support group member and the team attends a co-worker's wedding where Wilson's relationship with Sam takes an unexpected turn.