Mild to moderate hypertriglyceridemia usually results from multiple small-effect variants in genes that control triglyceride metabolism. Hypertriglyceridemia is a critical component of the metabolic syndrome but can also occur secondary to several other conditions or drugs. Hypertriglyceridemia frequently is associated with an increased risk of cardiovascular disease (CVD). Statins are the mainstay of CVD prevention in hypertriglyceridemia, but eicosapentaenoic ethyl esters should be added in very-high-risk individuals. Although fibrates lower triglyceride levels, their role in CVD prevention remains unclear. Familial partial lipodystrophy is another relatively rare cause, although its true incidence is unknown.