Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from high lipoproteins (HDLs) to triglyceride-rich lipoproteins (TRLs) in exchange for triglyceride. CETP forms a channel or tube between HDL and TRL allowing for this exchange. High levels of HDL cholesterol have been shown to be protective of the development of coronary heart disease (CHD). Patients with CETP deficiency have been reported, who have high levels of HDL cholesterol, and apparently enhanced longevity. Such findings prompted pharmaceutical companies to develop CETP inhibitors, and these agents are very effective in raising HDL cholesterol. Metabolic studies have documented that CETP inhibition in humans delays the fractional catabolism of HDL apolipoproteins (apo) A-I and A-II, while enhancing the fractional catabolism of TRL apoB-100 and apoE. CETP inhibition in humans dramatically increases HDL cholesterol and large HDL particles, while decreasing TRL cholesterol. No significant effects of CETP inhibition of fecal cholesterol excretion were noted. The CETP inhibitor torcetrapib has been tested in clinical trials evaluating carotid intimal medial thickness, coronary atherosclerosis as assessed by intravascular ultrasound, as well clinical endpoints. Excess mortality was observed in a large clinical trial in which torcetrapib and atorvastatin were compared with placebo and atorvastatin in patients with established CHD. Moreover, torcetrapib has been reported to form an unproductive“ complex with HDL and CETP,” as well as increasing aldosterone and blood pressure levels, while decreasing serum potassium concentrations. Other CETP inhibitors, specifically dalcetrapib and ancetrapib, have not been noted to have these latter effects. Clinical trials are going forward with dalcetrapib to determine whether this agent will reduce CHD risk in addition to statin therapy alone in patients with acute coronary syndrome. If clinical trials are positive, then CETP inhibitors will have an important place in the prevention of CHD.