During the past three decades, the protective role of omega (n)-3 polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid and docosahexaenoic acid, in patients with coronary heart disease has been widely reported. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) study, a large-scale clinical trial, recently showed that n-3 PUFA (850-882 mg/d) reduced mortality and admission to the hospital for cardiovascular reasons in patients with chronic heart failure (HF) who were already receiving recommended therapies. The favorable effects of n-3 PUFA in GISSI-HF suggest that marine fish oils could confer protection in HF mainly through their antiarrhythmic action and in part by influencing the mechanisms related to HF progression. This article reviews recent clinical and experimental evidence on the effect of n-3 PUFA in coronary heart disease, with particular attention on HF and its pathophysiologic mechanisms.