Apoptosis is a type of programmed cell death that is evident during embryonic development and normal tissue turnover. When the apoptotic activity extends beyond physiologic limits, it can determine and/or contribute to those pathologic states characterized by excessive cell loss and impairment of organ function. The clinical development of caspase inhibitors may represent a potential therapeutic strategy for influencing the onset and progression of ventricular dysfunction to terminal failure. This article focuses on the caspase cascade, a fundamental enzymatic system for apoptotic cell death. Caspases do not constitute the death signals, but are implicated in their transmission. These cytoplasmic cysteine proteases have a dual role in apoptosis. Caspases can operate as initiators, activating an endonuclease that catalyzes deoxyribonucleic acid fragmentation. Alternatively, caspases can act as effectors, participating in the total disassembly of cell structures. For example, apoptosis represents the principal form of myocyte death in the region of an acute myocardial infarction. In addition, apoptosis in the region bordering the infarct can influence the development of ischemic cardiomyopathy and ventricular dilation.