Omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and to a limited extent ω- 6 fatty acids: arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-GLA (DGLA), prevent cardiovascular disease, thrombosis and atherosclerosis, reduce cardiac arrhythmias, lower plasma cholesterol and triglycerides, lower high blood pressure and improve endothelial function. These beneficial actions of the fatty acids could be attributed to their ability to augment endothelial nitric oxide generation, inhibit HMG-CoA reductase and angiotensin converting enzyme (ACE) activities, block the production of pro-inflammatory cytokines, and modulate telomerase activity. AA, EPA, and DHA form precursors to anti-inflammatory molecules: lipoxins and resolvins that help in wound healing, inhibit the actions of pro-inflammatory eicosanoids, and suppress the production of free radicals and enhance nitric oxide (NO) generation. In addition, these fatty acids react with NO and NO-derived reactive nitrogen species to form nitroalkene derivative of fatty acids called as nitrolipids. Nitrolipids serve as potent ligands for peroxisome proliferator activated receptors (PPARs), inhibit platelet activation through elevation of cyclic AMP levels; suppress superoxide generation, degranulation, and integrin expression by human neutrophils, and induce vasorelaxation in a concentration dependent manner by releasing NO. Nitrolipids are formed at the sites of inflammation in significant amounts and increased by oxidative inflammatory reactions. Furthermore, ω-3 and ω -6 fatty acids interact with each other to enhance the formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators. Thus, GLA, DGLA, AA, EPA, and DHA when present in optimum amounts in the tissues, especially in endothelial cells, myocardium, platelets, and neutrophils, may aid in the prevention of cardiovascular diseases.