Several observational and experimental studies have proved polyunsaturated fatty acids N-3 (N-3 PUFA) beneficial effects.The first to be detected was the ipolipidic effect so these drugs have been used for the treatment of dislipidemic disorders, while antinflammatory, antithrombotic and antiarrhythmogenic effects have been found later. GISSI-Prevenzione trial proved the efficacy and tolerability of N-3 PUFA in post-myocardial infarction patients. According to this evidence-based findings, today N-3 PUFA are indicated for primary and secondary prevention of ischemic cardiopathy and sudden cardiac death (SCD). Moreover, as recently demonstrated in GISSI-HF trial and in other experimental studies, N-3 PUFA could be indicated in patients affected by chronic heart failure, in patients with implantable cardioverter defibrillators at high risk of SCD and, furthermore, for the prevention of atrial fibrillation after cardiac surgery. Large studies are in progress to confirm these relevant findings in patients at high cardiovascular risk.