The link between elevated plasma cholesterol levels and coronary atherosclerosis is now well established. During the past decade, results from therapeutic trials indicate that control of hypercholesterolemia does result in lower cardiovascular risk. Many of these results were obtained in hypercholesterolemic, middle-aged men. Comparable data in women are not available but it is inferred that they would also benefit from cholesterol reduction. Results from the Coronary Drug Project, extended over 15 years, indicate that lipid-lowering therapy with niacin for 5 years was associated with a decrease in total mortality as well as mortality from coronary heart disease. In the studies performed for shorter periods (5 to 7 years), therapy lowered only cardiovascular morbidity and mortality but had no beneficial effect on total mortality. A reduction in cardiovascular risk begins to appear 24 to 28 months after the initiation of therapy and continues to accrue thereafter. The relatively uniform results from recent large-scale clinical trials (Lipid Research Clinics Coronary Primary Prevention Trial, Coronary Drug Project, Helsinki Heart Study) indicate that cholesterol reduction, per se, probably explains the lower cardiovascular morbidity and mortality observed in these trials. As a result of these trials, recent redefinitions of hypercholesterolemia and more aggressive treatment programs have been recommended. These guidelines stress assessment of all cardiovascular risk factors and recommend individualized care of the patient. To control hypercholesterolemia, conservative measures with diet are recommended before therapy with medication is considered. Recent clinical trial experience indicates that the clinician can have significant impact on atherosclerosis by identifying and treating patients with plasma cholesterol levels in the high-risk range.