Patients with elevated triglycerides (TG) may be at a higher risk for cardiovascular (CV) disease. Omega-3 fatty acids (OM3FAs), particularly the long-chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), effectively reduce TG and thus may impact CV outcomes; however, clinical data have been inconsistent. This review discusses the efficacy, safety, and key considerations of currently approved prescription OM3FA products in patients with elevated TG with or without concomitant elevations in other atherogenic parameters. Currently, 6 prescription OM3FA formulations are approved in the United States: omega-3-acid ethyl esters (Lovaza, Omtryg, and 2 generic formulations), omega-3-carboxylic acids (Epanova), which contain both EPA and DHA, and icosapent ethyl (Vascepa), which is an EPA-only formulation. All prescription OM3FA products effectively lower TG, with the magnitude of TG reduction affected by baseline TG level. Products that contain DHA can raise levels of low-density lipoprotein cholesterol, which is of particular concern in patients with atherosclerosis; Vascepa, however, does not raise these levels and therefore provides these patients with another option. Long-term outcomes trials for Vascepa (ongoing) and Epanova (planned) will help clarify the potential CV benefits in patients with persistent hypertriglyceridemia despite statin therapy.