House (Hugh Laurie) and Cuddy (Lisa Edelstein) explore the ramifications admitting they have feelings for each other and attempt to make a real relationship work.

Meanwhile, due to a colleague's illness, Princeton Plainsboro is left without a neurosurgeon on site, threatening the hospital's accreditation as a Level 1 Trauma Center. As the team attempts treatment to get their sick colleague back to work, they discover there is more to the illness than they originally suspected and turn to House for direction. Instead, House remains elusive, leaving the team on its own in the season premiere episode of House.