Low levels of high-density lipoprotein cholesterol (HDL-C) in plasma are an independent coronary risk factor. Therapies that lower cholesteryl ester transfer protein (CETP) have preventative effects on aortic atherosclerosis in cholesterol-fed rabbits. CETP inhibitors are a new class of compounds that can increase HDL-C levels by up to 70%, according to data from phase I and II clinical trials. CETP inhibitors are therefore likely to be beneficial in patients with moderate hypercholesterolemia and HDL-C levels lower than 40 mg/dl. CETP inhibitors should, however, be viewed with caution as their effects on triglyceride metabolism are currently unknown.