Although the frequency of cardiovascular disease is declining, it remains a major present and future threat to health in the United States. The deleterious effects of abnormal blood lipid concentrations have long been recognized, but the benefit of corrective intervention in this process has only recently been demonstrated. We review the major lipid abnormalities and the available clinical therapeutic interventions. In addition, we discuss data that address the premise that reducing low-density lipoprotein cholesterol or raising high-density lipoprotein cholesterol should decrease the progression of coronary atherosclerosis, and we summarize drug trials in which clofibrate, niacin, cholestyramine, and gemfibrozil decreased coronary heart disease events. Studies that used cholestyramine and the combination of colestipol and niacin resulted in decreased progression of coronary artery disease. On the basis of early experience with lovastatin, inhibitors of hydroxymethylglutaryl-coenzyme A reductase are likely to be effective in the treatment of hypercholesterolemia. The available information on the association of low cholesterol levels and cancer suggests that low total cholesterol is a consequence rather than a cause of carcinoma. Current data strongly support the concept of vigorous intervention directed at management of lipids, both with non-pharmacologic treatment and with drug therapy, for the primary and secondary prevention of coronary atherosclerosis.