A prescription form of omega-3 fatty acids has been approved by the United States Food and Drug Administration as an adjunct to diet for the treatment of very high triglyceride levels. The active ingredients of omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are responsible for the triglyceride lowering. The prescription product contains a total of 0.84 g of these two active ingredients in every 1-g capsule of omega-3 fatty acids. The total EPA and DHA dose recommended for triglyceride lowering is approximately 2-4 g/day. Fish oil products containing EPA and DHA are available without a prescription, but the American Heart Association advises that therapy with EPA and DHA to lower very high triglyceride levels should be used only under a physician's care. In patients with triglyceride levels above 500 mg/dl, approximately 4 g/day of EPA and DHA reduces triglyceride levels 45% and very low-density lipoprotein cholesterol levels by more than 50%. Low-density lipoprotein cholesterol levels may increase depending on the baseline triglyceride level, but the net effect of EPA and DHA therapy is a reduction in non-high-density lipoprotein cholesterol level. Alternatively, patients may receive one of the fibrates (gemfibrozil or fenofibrate) or niacin for triglyceride lowering if their triglyceride levels are higher than 500 mg/dl. In controlled trials, prescription omega-3 fatty acids were well tolerated, with a low rate of both adverse events and treatment-associated discontinuations. The availability of prescription omega-3 fatty acids, which ensures consistent quality and purity, should prove to be valuable for the medical management of hypertriglyceridemia.