Necrosis and apoptosis are two forms of cell death in the myocardium that have been associated with ischemia and reperfusion. Although it has been well documented that necrosis, as a major form of myocyte cell death, rapidly leads to a destruction of a large group of cells after myocardial ischemia and reperfusion, the induction of apoptosis in myocardium, primarily triggered during reperfusion, may independently contribute to the extension of cell death (i.e. infarction) in a dynamic manner. Ischemic preconditioning (IP), an endogenous protective mechanism rapidly evoked by a brief period of ischemia, is recognized for its protection in limiting myocardial necrosis, but has also shown a profound inhibition in apoptosis. While much research has been done on the reduction of necrosis by IP, there remains no clear understanding of the time course of inhibition of apoptosis by IP after long-term reperfusion. In this review, we will show the time course of necrosis and apoptosis during reperfusion, focus on the role of apoptosis in the extension of lethal myocyte injury, and summarize the potential mechanisms involved in reducing apoptosis by IP. 'Classic' or 'early' IP has been shown to reduce apoptosis in part by inhibiting inflammatory cell activation and altering the expression of anti- and pro-apoptotic proteins as well as protein kinase C activity. It remains unknown, however, whether delayed IP participates in the attenuation of apoptosis in addition to necrosis. The demonstration of a 'window of opportunity' in inhibiting apoptosis by IP will provide new directions in research investigating mechanisms underlying myocyte cell death during reperfusion, and translate this information into new treatment approaches for reducing the extent of ischemia/reperfusion injury.