Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been shown to be effective at lowering low-density lipoprotein cholesterol and decreasing the risk of coronary heart disease. Although safe and well tolerated by most patients, statins have also been associated with muscle-related adverse events. This article reviews statin-associated myotoxicity to clarify the definitions of muscle-related adverse events and discusses their incidences in major statin trials, case reports, and review articles through January 2006. Milder complaints (ie, myalgia) are reported by approximately 5% to 7% of patients who take statins. More severe myotoxicity, namely rhabdomyolysis, is extremely rare for all statins save cerivastatin, and most recent estimates of its incidence are between 0.44 and 0.54 cases per 10 000 person-years. The mechanism of statin-associated myotoxicity has not been satisfactorily defined and is likely due to multiple factors, including membrane instability, mitochondrial dysfunction, and defects in myocyte duplication.