Epidemiologic studies have shown an inverse correlation between consumption of fish or other sources of dietary n-3 fatty acids and cardiovascular events. Numerous mechanisms of action for the favorable effect of dietary n-3 fatty acids on factors implicated in the pathogenesis of atherosclerosis have been described. Studies in dogs, swine, and nonhuman primates have consistently shown beneficial effects in various models of vasoocclusive diseases. Studies published currently do not indicate that dietary n-3 fatty acids prevent restenosis after percutaneous coronary angioplasty or induce regression of coronary atherosclerosis. However, in a recent study, occlusion of aortocoronary venous bypass grafts was reduced after 1 y by daily ingestion of 4 g fish-oil concentrate. In the Diet and Reinfarction Trial, 2-y overall mortality was reduced by 29% in survivors of a first myocardial infarction after consumption of n-3 fatty acid-rich fatty fish at least twice a week had been advised (Lancet 1989;2:757-61). When n-3 fatty acids were integrated into a diet resembling a traditional Mediterranean diet, 5-y cardiovascular mortality after a first myocardial infarction was reduced by 70% (Lancet 1994; 343:1454-9). Preliminary studies indicate that cardiac transplant patients could be an interesting focus of investigation. Currently, food sources rich in n-3 fatty acids are thought to be beneficial in secondary prophylaxis after a myocardial infarction. Large-scale clinical studies with endpoints such as morbidity and mortality are needed to more precisely define the role of n-3 fatty acids in primary and secondary prophylaxis of coronary atherosclerosis.