Cholesterol efflux is one of the essential events in cellular cholesterol homeostasis since peripheral cells do not catabolize the cholesterol molecule. There are two distinct mechanisms for the efflux. One is the non-specific classical pathway mediated by physicochemical diffusion of cholesterol through the aqueous phase and its esterification on high density lipoprotein (HDL) by lecithin: cholesterol acyltransferase (LCAT). The other is the specific and biological pathway in which new HDL particles are generated from cellular lipid by the direct interaction of cell membrane and amphiphilic apolipoproteins that have dissociated from HDL. The latter reaction consists of binding of apolipoprotein to the specific binding site of the cellular surface and subsequent mobilization of intracellular cholesterol for the HDL generation mediated by intracellular signal transduction. This reaction seems to be a major source of plasma HDL.