Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary lipid target. However, there has been increasing interest in raising high-density lipoprotein cholesterol (HDL-C) due to strong evidence linking low HDL-C levels with an increased risk of atherosclerosis. Raising HDL-C levels with lifestyle changes and pharmacologic interventions appear to reduce the risk of coronary artery disease beyond that of lowering LDL-C alone. Niacin has a substantial HDL-C raising effect, and also may beneficially alter total cholesterol, LDL-C and triglyceride levels. Niacin also exhibits antioxidant, anti-inflammatory and other beneficial effects on atherosclerosis. Niacin is safe and effective to use in women, in patients with diabetes mellitus and/or metabolic syndrome, and when used in combination with statins. Niacin has the promise of being a powerful pharmacologic agent in the fight against atherosclerotic disease, although additional clinical studies are required to examine this further.