Dr. Gregory House (Hugh Laurie) has spent his career taking on seemingly hopeless cases, but when his rapport with Dr. Lisa Cuddy (Lisa Edelstein) changes, he finds himself facing new -- and very different -- challenges. His team at Princeton-Plainsboro Teaching Hospital (Omar Epps, Jesse Spencer, Peter Jacobson, Robert Sean Leonard, Amber Tamblyn and Olivia Wilde) also continues to blaze trails as they investigate baffling medical cases involving a religious zealot, a professional bull rider and possibly even smallpox.