The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are a well-tolerated, effective class of medications for the reduction of low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. Extensive data from clinical trials demonstrate that these agents reduce fatal and nonfatal cardiovascular risk in primary and secondary prevention patients, including women and the elderly. A threshold value for LDL-C reduction below which there is no further clinical benefit has not yet been identified. In the Heart Protection Study (HPS), significant relative risk reduction occurred even among patients with LDL-C levels < 2.6 mmol/l (100 mg/dl). Statin therapy also produced reductions in cardiovascular disease in a wide range of high-risk patients regardless of baseline cholesterol levels. Rhabdomyolysis, typically defined as muscle pain or weakness associated with creatine kinase levels higher than 10 times the upper limit of normal and the presence of myoglobulinuria, is a rare but potentially serious complication of statins. Although dose-dependent transaminase elevations occur in 0.5 to 2% of cases, it has not been determined whether these elevations qualify as true drug-related hepatotoxicity. Management of myopathy and elevated transaminases is addressed in a joint publication from the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI). Because statins have significant potential benefits and a low risk for serious adverse effects, aggressive therapy should be considered in patients at high risk for coronary heart disease.