The major aspects of the antithrombogenic and antiatherogenic effects of polyunsaturated fatty acids (PUFA) have been outlined. After briefly relating on the biochemistry, the essentiality concept has been defined. Some of the many evidences of their effects both on men and animals have been reported. Eicosanoid metabolism is discussed and eicosanoid compounds derived from omega-6 and omega-3 fatty acids are compared with regard to their effects concerning atherosclerosis. Considerations about the correct amount of PUFA are reported as tentative strategies for a cardiovascular protective diet.