BACKGROUND: Moderate hypertriglyceridemia is fairly common, and elevated triglycerides are a risk factor for coronary heart disease. The omega-3 fatty acids EPA and DHA have been shown to lower triglycerides in many clinical studies. Prescription omega-3 fatty acid concentrates (P-OM3) are indicated for use in people with very high triglycerides (> 500 mg/dl). Current guidelines recommend that triglycerides should be less < 150 mg/dl. OBJECTIVE: This review provides an overview of the use of omega-3 concentrates (both P-OM3 and over-the-counter fish oil) to lower triglycerides in people who have moderate hypertriglyceridemia (triglycerides in the range of 150 - 500 mg/dl). The objectives were to examine clinical evidence, describe the magnitude of effects and predict future clinical use of P-OM3. METHODS: Published, peer-reviewed studies of omega-3 concentrates were included if they were placebo-controlled, double-blind, of sufficient size to demonstrate triglyceride lowering, and studied a population described as having a mean baseline triglyceride value of 150 - 500 mg/dl. Studies using the 4-g dose of P-OM3 were used to develop a model of percent triglyceride lowering as a function of baseline levels. RESULTS/CONCLUSIONS: P-OM3 are effective in reducing triglycerides by approximately 30% in this population and are likely to be combined with other drugs (e.g., statins) to treat combined dyslipidemia.