Coronary events often result from thrombi that form because of physical disruption of the atherosclerotic plaque. The dynamic nature of the plaque offers the opportunity to intervene to modify plaque biology with lifestyle changes and, if needed, pharmacologic measures. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce levels of serum cholesterol and decrease the incidence of coronary events, but some of the benefits of statins may not depend on their effects on circulating lipids. Indeed, increasing evidence suggests that statins may also enhance plaque stability. Such evidence includes results of preclinical studies with experimental atherosclerosis as well as imaging data and analyses of proinflammatory and prothrombotic mediators in clinical trials. Currently, however, no studies have demonstrated conclusively the mechanisms underlying the unexpected magnitude and rapidity of statin benefits. This article reviews the evolution of the concept of plaque stabilization and reexamines the evidence for the role of statins in that process.