Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the genomes of all higher eukaryotes. The mechanisms involved in apoptosis suggest that the process is based on a viral defense originally developed in primitive multicelled eukaryotes and that the fundamental execution platform of the process involves 1) inhibition of protein synthesis at the level of translation initiation, 2) proteolysis specifically involving degradation of DNA repair mechanisms, and 3) polynucleotide degradation. In mammals this execution platform is regulated by a complex molecular signaling system that includes feedback mechanisms tending toward activation of all elements of the execution platform if only one element is initially engaged. Tissue ischemia and reperfusion activate elements of the apoptosis system, which thus represents a therapeutic target for emerging treatment approaches to preserve cellular integrity in critical organs such as the heart and brain.