Members of the caspase family of aspartate-specific cysteine proteases are best known for their involvement in apoptosis (human caspases 2, 3, 6, 7, 8, 9, 10; mouse caspases 2, 3, 6, 7, 8, 9, 12) and the maturation of cytokines such as IL-1ß and IL-18 (human caspases 1, 4, 5; mouse caspases 1, 11; Thornberry and Lazebnik 1998; Shi 2002). Recently, however, there have been a number of reports suggesting that caspases, in particular caspase 8, may have an additional role in the immune system promoting lymphocyte activation and proliferation (Chun et al. 2002; Salmena et al. 2003). The seemingly paradoxical observations that caspase 8 is critical for both activation and death of cells of the immune system are the focus of this review.