Non-high-density lipoprotein (non-HDL) cholesterol level is determined by subtracting the high-density lipoprotein cholesterol level from the total cholesterol level and thus encompasses not only low-density lipoprotein cholesterol, but also the cholesterol contained in atherogenic, triglyceride-rich particles like remnants. This review summarizes data extracted from English-language publications accessible through MEDLINE on the population distribution of non-HDL cholesterol, its relationship to cardiovascular disease, and the potential benefits of treatment. Non-HDL cholesterol levels in the population vary by age, sex, and race and are closely linked to measures of obesity, especially visceral obesity. Several studies in populations with and without cardiovascular disease show that non-HDL cholesterol levels relate to atherosclerosis severity and subsequent cardiovascular morbidity and mortality. Preliminary data also suggest that pharmacologically induced changes in non-HDL cholesterol levels relate to prognosis. In the National Cholesterol Education Program Adult Treatment Panel III report, non-HDL cholesterol has been designated a secondary target of therapy among patients with hypertriglyceridemia.