Apoptosis occurs in a wide variety of physiological settings and diseases, including cardiovascular diseases. The fact that features of both apoptosis and necrosis are found in cardiomyocyte death following ischemia/reperfusion (I/R) has prompted research into ways of blocking specific events of apoptosis. In isolated cardiomyocytes, reduction of intracellular acidification or calcium accumulation, activation of vacuolar proton ATPase, and inhibition of caspases appear to exert a protective effect, but whether this would translate into preservation of the myocardium after I/R in vivo remains to be determined. The apparent "bottleneck" provided by caspase activation in apoptosis is the current target of antiapoptotic interventions, but other potential targets need to be investigated, such as the Bcl family proteins, or preconditioning. The hypothesis that inhibition of the caspase cascade will reduce ischemic injury remains to be tested in vivo. A direct causal connection between apoptosis and progressive myocyte loss in congestive heart failure has yet to be established. However exciting the prospects of therapeutic interventions based on modulation of apoptosis may be, we should nevertheless be on the lookout for unexpected adverse reactions...