Results of primary and secondary prevention trials have shown that lowering total cholesterol and low-density lipoprotein (LDL) cholesterol leads to a reduction in both fatal and nonfatal ischemic events. The reduced coronary artery disease (CAD) risk associated with cholesterol lowering appears to be unrelated to the intervention used, whether it be a low-fat/low-cholesterol diet, partial ileal bypass surgery, or pharmacologic intervention with an agent such as a bile resin, a fibrate, or niacin. Data emerging on the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have shown that this newest class of cholesterol-lowering agents also reduces the risk for CAD. The studies provide increasing evidence that high LDL cholesterol levels not only contribute to atherosclerotic plaque formation but also interfere with normal endothelial control of arterial vasomotor tone. Because the small amount of plaque regression observed on angiographic studies is not sufficient to explain the magnitude of CAD risk reduction associated with lowered levels of LDL cholesterol, these studies suggest that vasomotor control and plaque stabilization may have a greater impact on clinical events than the stenosis caused by atherosclerotic plaques.