The failing heart is characterized by an increase in chamber volume and a reduction in wall thickness, leading to marked reduction in the mass-to-chamber volume ratio. These changes result from extensive myocyte loss, compensatory myocyte hypertrophy, and remodeling of the interstitial compartments. Myocyte loss in heart failure appears to result from the combined effect of myocyte necrosis and apoptosis. DNA strand breaks—the hallmark of apoptosis—have also been recently demonstrated in normal cardiac aging and myocardial infarction. Apoptosis is activated by ischemia and mechanical stress. Reactive oxygen species, atrial natriuretic peptide, angiotensin II, tumor necrosis factor–α, the Fas molecule, and cell-cycle reentry appear to play a role in this process. Intracellular molecular control mechanisms of apoptosis have been evidenced, suggesting therapeutic strategies to prevent apoptosis with a view to increasing survival in patients with cardiac diseases...