Omega-3 polyunsaturated fatty acids have been effective in reducing cardiovascular mortality in the recent GISSI-Prevenzione study. In a post-hoc analysis of this study an important observation has been the reduction of sudden cardiac death. The hypothesis that a protection from sudden death occurs because of antiarrhythmic effects of omega-3 fatty acids is supported by studies on cellular and animal models. A few intervention studies before the GISSI-Prevenzione and several retrospective analyses of epidemiological studies, in which nutritional variables connected with the intake of omega-3 fatty acids had been recorded, also support such a hypothesis. This review critically summarizes this type of evidence and indicates current research directions for its further validation.