Interest in the cardiovascular protective effects of n-3 (omega-3) fatty acids has continued to evolve during the past 35 y since the original research describing the low cardiovascular event rate in Greenland Inuit was published by Dyerberg et al. Numerous in vitro experiments have shown that n-3 fatty acids may confer this benefit by several mechanisms: they are antiinflammatory, antithrombotic, and antiarrhythmic. The n-3 fatty acids that have received the most attention are those that are derived from a fish source: namely, the longer-chain n-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). More limited data are available on the cardiovascular effects of n-3 fatty acids derived from plants such as alpha-linolenic acid (ALA; 18:3n-3). Observational data suggest that diets rich in EPA, DHA, or ALA do reduce cardiovascular events, including myocardial infarction and sudden cardiac death; however, randomized controlled trial data are somewhat less clear. Several recent meta-analyses have suggested that dietary supplementation with EPA and DHA does not provide additive cardiovascular protection beyond standard care, but the heterogeneity of included studies may reduce the validity of their conclusions. No data exist on the potential therapeutic benefit of EPA, DHA, or ALA supplementation on those individuals who already consume a vegetarian diet. Overall, there is insufficient evidence to recommend n-3 fatty acid supplementation for the purposes of cardiovascular protection; however, ongoing studies such as the Alpha Omega Trial may provide further information.