Low levels of high-density lipoprotein cholesterol (HDL-C) are currently considered to be a major risk factor for the development of coronary artery disease (CAD). Deficiencies in the HDL metabolic pathway promote atherosclerosis and contribute to CAD. Low HDL-C levels are included in the Framingham 10-year risk assessment for CAD although they are not yet targeted for therapy. Recent clinical trials have shown benefits from raising HDL-C, particularly in patients with lower baseline levels. The statin class of drugs, used primarily to lower the level of low-density lipoprotein-cholesterol, may be able to raise the HDL-C level as well. Statins could potentially affect HDL-C by different modes of action, most importantly by altering reverse cholesterol transport. Among the currently available statins, simvastatin has demonstrated the most consistent ability to raise HDL-C level, but further large-scale studies at an early stage will be needed to prove the antiatherogenic effects of this class of drugs.