Bcl-2 family proteins serve as critical regulators of pathways involved in apoptosis, acting to either inhibit or promote cell death. Altered expression of these proteins occurs commonly in human cancers, contributing to neoplastic cell expansion by suppressing programmed cell death and extending tumor cell life span. Moreover, because chemotherapeutic drugs typically exert their cytotoxic actions by inducing apoptosis, the ultimate efficacy of most anticancer drugs can be heavily influenced by the relative levels and state of activation of members of the Bcl-2 family. The question of how Bcl-2 family proteins function remains debatable, but new findings are shaping our impressions of these multi-functional proteins and revealing the details of how these proteins participate in the regulation of cell life and death.