Since the discovery of 4-1BB 15 years ago, the receptor and its ligand (4-1BBL) have remained enigmatic molecules because of their highly regulated pattern of expression. Classically, 4-1BB is known to function as a costimulator for T cells and as a potent survival factor for CD8⁺ T cells. Recent studies highlight the participation of 4-1BB and its ligand 4-1BBL in a more complex network of immune cell responses and suggest that intervening in the 4-1BB costimulatory pathway might have some potential as a therapeutic approach to immune disorders.