Recent work has demonstrated that oncogenes and tumor suppressor proteins regulate apoptotic cell death. Current efforts are therefore directed at determining how they exert their effects. It appears that oncogenes can control activation of the apoptosis endonuclease(s) either by regulating the signal(s) that trigger the process or via effects on expression and/or activation of key components of the effector machinery, including the endogenous endonuclease itself. This article summarizes the available information on the biochemical mechanisms underlying the effects of oncogenes on endogenous endonuclease activation and presents models to explain the observation that they also regulate alternative cell fates such as cell proliferation and differentiation.