Inhibition of cholesteryl ester transfer protein (CETP) has the ability to increase high-density lipoprotein (HDL)-cholesterol levels and potentially reduce cardiovascular risk. The first CETP inhibitor, torcetrapib, was discontinued due to off-target effects resulting in increased mortality. However, anacetrapib does not appear to exhibit these effects and is being developed as a selective inhibitor of CETP to be orally administered for the treatment of primary hypercholesterolemia and mixed hyperlipidemia.Areas covered are: mode of action, preclinical development and clinical trials of anacetrapib, a CETP inhibitor. The article provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of anacetrapib and insight into its clinical efficacy and safety. In clinical trials, anacetrapib produced dose-dependent elevations in HDL-cholesterol and reductions in low-density lipoprotein (LDL)-cholesterol. Furthermore, anacetrapib has been shown to increase apolipoprotein (apo) A-I and decrease apoB levels.Anacetrapib is a potent, reversible CETP inhibitor that is not only able to increase HDL-cholesterol, but also further decrease LDL-cholesterol when taken in combination with a statin. Safety and tolerability studies reported to date are promising. The results from Phase III trials investigating the efficacy of anacetrapib for the prevention of major coronary events in patients with atherosclerotic cardiovascular disorders are awaited with interest.