Clinical trial evidence strongly favors aggressive risk factor modification in the prevention of coronary artery disease (CAD). The latest landmark trial of therapy using a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) is the Heart Protection Study (HPS) of simvastatin versus placebo in a cohort of patients at high risk for CAD. The HPS reported a number of highly significant reductions in the risk for major vascular events with treatment. It also provides new insights into the effects of statin therapy in patient subgroups, such as the elderly, women, and those with noncoronary vascular disease. These data are likely to have an important influence on the future of cardiovascular disease prevention.