A clinicopathological synthesis is presented of the relationship of ischemic heart disease to sudden cardiac death. The immediate pathophysiological process responsible for sudden cardiac death is a lethal arrhythmia, usually ventricular fibrillation. Although significant coronary atherosclerosis is present in most cases of naturally occurring sudden death, available evidence indicates that several mechanisms can be operative in the pathogenesis of the fatal event. These are (1) acute myocardial infarction in a minority of cases; (2) myocardial ischemia, without infarction, which is initiated either by (a) an exertion-induced increase in myocardial oxygen demand or (b) an acute coronary event often involving plaque degeneration and platelet aggregation; and (3) a primary arrhythmia, usually resulting from altered electrical conduction in the setting of a previous myocardial infarction.