Despite an increased understanding of risk factors for cardiovascular disease and the development of new programs, procedures, and medications to reduce risk, effective large-scale primary and secondary prevention have remained difficult to achieve. Large-scale, primarily educational, community-based programs aimed at detecting and reducing risk can be effective, particularly when they are aimed at specific populations at increased risk. However, the long-term benefits of these programs have been modest. Recent studies have demonstrated that lipid-lowering therapy is a critical adjunct to dietary and lifestyle changes. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in particular are highly effective in reducing cardiovascular risk in both primary and secondary prevention programs that combine lifestyle modification and aggressive medical therapy. The ability of these drugs to produce rapid improvements in endothelial function and increase coronary perfusion also supports their use in the medical rather than surgical management of at least some patients with cardiovascular disease who are candidates for percutaneous transluminal coronary angioplasty.