Various genetically encoded programs involved in the signaling, initiation, and execution of cell death decide cells׳ fate during development and adult life. These programs can execute physiological cell death during development or tissue turnover, and are also involved in the inappropriate elimination of cells under pathological conditions. Because balanced cell turnover is essential for life, defects in cell elimination can also result in disease, the foremost example being cancer. In many circumstances, both physiological cell death and cell death in pathological settings have similar morphological and biochemical characteristics. Perhaps the best-characterized biochemical and morphological changes during a cell death program are those defined as apoptosis. Apoptosis is characterized by condensation and fragmentation of the nucleus with shrinkage of the cytoplasm and exposure of surface molecules that facilitate recognition of the dying cells by phagocytes. However, other types of cell death are present and are strictly regulated in vivo, including cell lysis/necrosis or autophagy. Imbalance in cellular calcium regulation has been involved in both apoptotic and nonapoptotic cell death. Calcium can be a signal for cell death or simply a downstream consequence of the activation of the death machinery.