Apoptosis and necrosis are two fundamental types of cell death. Current knowledge indicates that the key mechanism of apoptosis is endonuclease activation leading to internucleosomal double-stranded chromatin (DNA) breaks, whereas the key mechanism of necrosis is cell membrane damage. The initial alterations of cellular metabolism and electrolyte homeostasis induced by an injurious agent may activate at least four major pathways leading to loss of membrane integrity: membrane phospholipid degradation, production of amphipathic lipids, damage to the cytoskeleton, and generation of toxic oxygen species and free radicals. These insights point the way for further research to establish definitive causes of specific types of cell injury and cell death, and they provide important clues for the design of improved diagnostic approaches and therapeutic interventions.