The cardioprotective effects of food rich in omega-3 (ω-3) polyunsaturated fatty acids (PUFA) on cardiovascular risk has been of interest from the moment when a low rate of coronary heart disease was documented in the Eskimo population. The aim of the present review is to discuss recent studies documenting multidirectional action of ω-3 PUFA due to its pleiotropic properties. Experimental studies in cellular and animal models have extensively documented the favorable effects of ω-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) on: inflammatory processes, endothelial dysfunction, platelet aggregation and arrhythmogenesis. It was reported that antiarrhythmic effects of ω-3 PUFA resulted from stabilization of cardiomyocyte membrane and inhibition of ion channels. Moreover, PUFA possess several pleiotropic properties i.e. anti-inflammatory, anti-atherogenic and antithrombotic. Anti-atherogenic effects (plaque stabilization) of ω-3 PUFA have recently been demonstrated. It was documented (OCEAN study) that eicosapentaenoic acid from a source of highly purified ethyl esters is incorporated into plaques in a relatively short period of time and these higher concentrations of ω-3 PUFA may stabilize vulnerable atherosclerotic plaques. The anti-inflammatory effect of ω-3 PUFA is associated with reduction of levels of TNF-α and interleukin-6. Eicosapentaenoic acid and docosahexaenoic acid inhibit arachidonic acid metabolism to inflammatory eicosanoids.