Plasma cholesterol transfer protein (P-CETP) plays a central role in cholesterol metabolism by pronroting transfer of cholesteryl esters from high density lipoprotein (HDL) to very low density lipoproteins in exchange for triglycerides. The CETP-reaction may hereby be a critical factor in reverse cholesterol transport, i.e., the transfer of cholesterol from peripheral tissues to the river for catabolism. Human genetic CETP deficiency is associated with increased P-HDL-cholesterol, whereas CEPT transgenic mice display decreased P-HDL-cholesterol. The effects of CETP on atherogenesis are currently unpredictable, and they are likely to depend on the metabolic context. However, the presence of specific polymorphisms in the CETP gene may be of clinical importance, and CETP should be considered among the factors relevant for differentiation of dyslipidemic syndromes associated with susceptibility to and protection from atherosclerotic disease.