House suffers head trauma and short-term memory loss after being involved in a bus crash. While his colleagues urge him to rest, House is plagued by the belief that he noticed someone with a life-threatening illness on the bus, but cannot remember who they were.

House and his team struggle to save Amber's life following the bus crash. As problems in her heart begin to affect her other major organs, House agrees to Wilson's request to cool Amber's body to buy time for a diagnosis.