The role of omega-3 polyunsaturated fatty acids (PUFAs) in the secondary prevention of cardiovascular disease has recently been debated. The GISSI-Prevention trial demonstrated that supplementation with 1 g/day of eicosapentaenoic acid plus docosahexaenoic acid (EPA/DHA) was associated with a reduction in all-cause and cardiovascular mortality in patients with myocardial infarction. However, some subsequent meta-analyses, though not without methodological flaws, did not confirm the beneficial effect on cardiovascular mortality. More evidence has recently become available from the analysis of "real-world" data that point to the effectiveness of PUFA supplementation in reducing cardiovascular events in patients with recent acute coronary syndrome. Meantime, in the determination no. 94 by the Italian Medicines Agency (AIFA), reimbursement of PUFAs containing at least 85% of EPA and DHA has been recognized for 12 months in patients with acute coronary syndrome and ejection fraction >40% and for 18 months in those with ejection fraction ≤40%.