A growing number of trials that used fibrates and niacin alone or in combination with other lipid-altering agents have shown that both these drugs are effective for reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and for increasing high-density lipoprotein cholesterol (HDL-C) levels. These lipid changes are associated with a reduction in events such as fatal and nonfatal myocardial infarction, stroke, and transient ischemic attack. In angiographic trials, they are associated with disease regression, increased minimal luminal diameter, and protection from risk of new lesions. In a head-to-head comparison study, niacin 2,000 mg/day increased HDL-C more than gemfibrozil 1,200 mg/day, and decreased the total cholesterol-to-HDL-C ratio, lipoprotein (a) (Lp[a]), and fibrinogen levels significantly more. Combination therapies of niacin plus a resin or statin are effective, well tolerated, and safe.