Apoptosis plays a key role in the pathogenesis in a variety of cardiovascular diseases due to loss of terminally differentiated cardiac myocytes. Cardiac myocytes undergoing apoptosis have been identified in tissue samples from patients suffering from myocardial infarction, diabetic cardiomyopathy, and end-stage congestive heart failure. Apoptosis is a highly regulated program of cell death and can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic reticulum. The cell death program is activated in cardiac myocytes by various stressors including cytokines, increased oxidative stress and DNA damage. Many studies have demonstrated that inhibition of apoptosis is cardioprotective and can prevent the development of heart failure. This review provides a current overview of the evidence of apoptosis in cardiovascular diseases and discusses the molecular pathways involved in cardiac myocyte apoptosis.