Apoptosis, a genetically programmed mechanism of eliminating cells in response to a variety of stimuli, provides protection against cancer and viral infections as well as maintenance of homeostasis in living organisms. Two classes of molecules, the Bcl-2 family of regulators and the ICE family of proteases, have emerged from different vertebrate, invertebrate and viral systems that have been used to elucidate the pathways leading to apoptosis. However, no connection between these two disparate families of apoptotic regulators has been convincingly established. In reviewing the recent advances pertaining to the Bcl-2 and ICE-related protein families, one can address the question of a functional relationship between the two classes of proteins.