Apoptosis has long been recognized as an important event in the heart during fetal development. It is becoming increasing clear, however, that mature cardiomyocytes retain vestiges of the same programmed cell death machinery utilized by the fetal heart and that this cell suicide mechanism can be inappropriately triggered during myocardial infarction, chronic heart failure, sepsis, allograph rejection, and other pathological conditions that affect the heart. This article, I discusses some of the mechanisms involved in the execution of apoptosis and the families of proteins that regulate it. Though our understanding of the role of apoptosis in diseases of the cardiovascular system is still in its infancy, recent findings hint that many of the cell death molecules previously implicated in other diseases are indeed at play in the adult heart during times of pathology. Further elucidation of the specific mechanisms relevant to the heart will undoubtedly reveal new strategies for preventing cardiomyocyte cell death and improving outcome for patients with heart disease.