This chapter discusses the chemistry, metabolism, and biological properties of omega-3-fatty acids (ω-3 PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Specifically, the current state of knowledge on effects of ω-3 PUFAs on plasma lipids, atherosclerosis, metabolic syndrome and diabetes, and obesity, platelet function, blood pressure and cardiac arrhythmia at molecular level is provided. This review also discusses the evidence from basic and clinical studies that propose the use of ω-3 PUFAs as an adjunct therapy in the treatment of cardiovascular disease (CVD). The use of ω-3 PUFAs in CVD may be recommended, but caution should be kept in mind when used with other drugs.