We reviewed the available evidence on the cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) intake, focusing on long-chain (seafood) n-3 PUFA, including its major food sources, effects on physiological risk factors, possible molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and available dietary guidelines. Major food sources include lipid-rich fish and other seafood. Ingestion of n-3 PUFA reduces plasma triglycerides, resting heart rate and blood pressure, potentially improving myocardial perfusion and efficiency, decreasing inflammatory response and improving vascular function. Experimental studies have demonstrated a direct2 antiarrhythmic effect of n-3 PUFA, which questions the existing literature on humans. n-3 PUFA affects a myriad of molecular pathways, including alteration of the physicochemical properties of cell membranes, direct interaction and regulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in the arachidonate histotype and the conversion of n-3 PUFA to biologically active metabolites. In prospective observational studies and adequate clinical randomized trials, the benefits of n-3 PUFA appear to be most associated with coronary heart disease mortality and sudden cardiac death. The potential impact of n-3 PUFA on the prognosis of other cardiovascular events is less well established, including observational studies and/or randomized trial evidence on the effects of n-3 PUFA on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, frequent ventricular arrhythmias, and heart failure. of conflicting evidence. Gaps in research include the relative importance of different physiological and molecular mechanisms, the exact dose response of physiological and clinical effects, whether fish oil represents all the benefits of fish consumption, and the clinical effects of plant-based n-3 PUFA. In conclusion, the current data provide consistent and strong evidence that n-3 PUFA are biologically active compounds that reduce the risk of sudden cardiac death. National and international guidelines consistently recommend that the general population consume 250 mg of long-chain n-3 PUFA daily or at least two servings of oil-rich fish per week.