It has been suggested that apoptosis may be responsible for a significant amount of cardiomyocyte death during acute myocardial infarction as well as for a progressive loss of surviving cells in failing hearts. Typical apoptosis can indeed be induced in cardiomyocytes at the experimental conditions. In actual heart diseases, in contrast, there is very little direct morphological evidence of apoptosis in cardiomyocytes occurring at any stage of myocardial infarction and heart failure, despite the availability of much indirect evidence that includes detection of DNA fragmentation and apoptosis-related factors. For that reason, the potential efficacy of therapeutic intervention to prevent apoptosis remains controversial. This review will survey available data from both animals and humans to critically assess the role of cardiomyocyte apoptosis during myocardial infarction and its relevance to myocardial remodeling and during progression to heart failure. Also considered will be nonmyocyte interstitial cells, which have received less attention than myocytes despite definitive evidence of their apoptosis in the infarcted heart and recent studies suggesting that blockade of apoptosis among these cells mitigates postinfarction cardiac remodeling and heart failure. We conclude from our survey that there are many hurdles to surmount before regulation of apoptosis can be clinically applied in the treatment of myocardial infarction and heart failure.