Omega-3 fatty acids (Poly-Unsaturated Fatty Acids or PUFA n-3) have been initially found to reduce plasma levels of triglycerides and to increase levels of high-density lipoprotein in patients with marked hypertriglyceridemia. However, in both bench research studies and clinical trials, omega-3 fatty acid intake has recently been associated with an anti-arrhythmic efficacy. At experimental level, n-3 PUFA administration produces several actions on ionic channels regulating transmembrane action potential. At clinical level, the most significant finding was the reduction in the incidence of sudden death in survivors of MI in the Gruppo Italiano per lo Studio della Sopravvivenza nellInfarto Miocardico (GISSI)-Prevention trial and the subsequent recommendation for administration of fish oil as part of the post-infarction regimen in European guidelines. More recently, Omega-3 fatty acids administration has been associated with a lower incidence of atrial fibrillation in patients who underwent cardiac surgery. Contrasting results have been instead reported in patients with implantable cardioverter defibrillators. This article reviews in detail the basic and clinical research studies of fish oil as an anti-arrhythmic entity, the types of arrhythmias that have been beneficially affected by fish oil administration, and the presumed and known mechanisms by which the beneficial actions are exerted.