Given the crucial role of apoptosis in such a diverse array of physiologic func tions, it is no surprise that aberrations of this process underlie a host of develop mental, immune, degenerative, and neoplastic disorders. This appreciation has fueled a furious investigation of the molecular determinants and mechanisms of apoptosis and a search for the key regulators of this process (Hengartner, 2000). The molecular execution of cell death involves activation of members of a family of cysteine-dependent aspartate-specific proteases (caspases) by two major mecha nisms. One mechanism, termed the ‘intrinsic’ pathway, signals the release of prodeath factors from the mitochondria via the action of pro-apoptotic members of the Bcl-2 family (Green and Reed, 1998; Gross et ah, 1999a; Green, 2000). An alternative mechanism of activating caspases and mitochondrial disruption, termed the ‘extrinsic’ pathway, is triggered by engagement of cell-surface ‘death receptors’ by their specific ligands (Ashkenazi and Dixit, 1998).