The use of FDA-approved niacin (nicotinic acid or vitamin B3) formulations at therapeutic doses, alone or in combination with statins or other lipid therapies, is safe, improves multiple lipid parameters, and reduces atherosclerosis progression. Niacin is unique as the most potent available lipid therapy to increase high-density lipoprotein (HDL) cholesterol and it significantly reduces lipoprotein(a). Through its action on the GPR109A receptor, niacin may also exert beneficial pleiotropic effects independent of changes in lipid levels, such as improving endothelial function and attenuating vascular inflammation. Studies evaluating the impact of niacin in statin-naïve patients on cardiovascular outcomes, or alone and in combination with statins or other lipid therapies on atherosclerosis progression, have been universally favorable. However, the widespread use of niacin to treat residual lipid abnormalities such as low HDL cholesterol, when used in combination with statins among patients achieving very low (<75 mg/dL) low-density lipoprotein cholesterol levels, is currently not supported by clinical outcome trials.