Apoptosis is a rediscovered mechanism of cell death crucial in normal development. Recent exploration of the genetic mechanisms of apoptosis has broadened our insight into the regulation of cell death in development as well as disease states. We present an overview on current understanding of the genetic molecular events in apoptosis in all, or most cell types, with emphasis on events observed in a well-characterized model of neuronal death in vitro. The second part of this article reviews recent studies in in vivo stroke models on the mechanism of cell death relevant to apoptosis after cerebral ischemia. Further delineation of the mechanisms of cell death, especially those that trigger apoptosis, is likely to redirect our approaches in the development of new therapeutic interventions for ischemic stroke.