Abstract: Omega-3 fatty acids (omega-3 PUFAs) are essential fatty acids in human tissues. Substantial research suggests that Omega-3 exerts a protective effect on cardiovascular system. However, the molecular mechanism is still unclear. Eicosapentenoic acid (EPA) and docosahexenoic acid (DHA) are two kinds of omega-3 PUFAs from fish oils, which have been cited for prevention and treatment of cardiovascular diseases. This paper reviews the basic characteristics of omega-3 PUFAs and their molecular mechanisms of mediating or modulating protective effects on the cardiovascular system.