The n-3 fatty acids of fish and fish oil have great potential for the prevention and treatment of patients with coronary artery disease. Unlike many of the pharmaceutical agents used in patients with coronary artery disease that have just a single mechanism of action, the eicosapentaenoic and docosahexaenoic acids of fish oil have multifaceted actions. One of their most important effects is the prevention of arrhythmias, with documentation derived from experiments in cultured myocytes, experiments in animals, epidemiologic correlations, and clinical trials. Especially important is the ability of these n-3 fatty acids to inhibit ventricular fibrillation and consequent cardiac arrest. Eicosapentaenoic acid has several antithrombotic actions, particularly in inhibiting the synthesis of thromboxane A2, the prostaglandin that causes platelet aggregation and vasoconstriction. Fish oil retards the growth of the atherosclerotic plaque by inhibiting both cellular growth factors and the migration of monocytes. The n-3 fatty acids promote the synthesis of the beneficial nitric oxide in the endothelium. Experiments in humans indicate a profound hypolipidemic effect of fish oil, especially lowering of plasma triacylglycerol. Both very-low-density lipoprotein production and apolipoprotein B synthesis are inhibited by fish oil. Finally, fish oil has a mild blood pressure-lowering effect in both normal and mildly hypertensive individuals. These composite effects suggest a prominent therapeutic role for fish oil in the prevention and treatment of coronary artery disease.