Plasma high-density lipoproteins (HDL) consist of about 50 percent protein and 50 percent lipids. The principal apolipoproteins of HDL, apo A-I and apo A-II, are synthesized in the liver (apo A-I and apo A-II) or small intestine (apo A-I), secreted as components of triglyceride (TG)-rich lipoproteins (TRL), and then transferred into HDL during lipolysis, along with phospholipid and cholesterol. Alternatively, they may be secreted as free apoproteins, then acquire lipids by interaction with the cellular ATP binding cassette transporter, ABC1. The plasma cholesterol-esterifying enzyme lecithin: cholesterol acyltransferase (LCAT) circulates bound to HDL and uses free cholesterol and phospholipids as substrates in the generation of cholesteryl esters (CE). HDL also contains a phospholipid transfer protein (PLTP) and a cholesteryl ester transfer protein (CETP), which mediate the transfer of phospholipid and cholesterol into HDL and the removal of cholesteryl esters from HDL, respectively. CETP mediates a hetero-exchange of HDL CE for TG of TRL, and the HDL TG is subsequently hydrolyzed by hepatic lipase (HL). The coordinate activities of PLTP, CETP, LCAT, and HL promote the formation and turnover of HDL CE, which is a central event in the transport of cholesterol from peripheral tissues to the liver, that is, reverse cholesterol transport. The return of plasma HDL CE to the liver may involve transfer to TRL by CETP, selective uptake of free and esterified cholesterol (i.e., cellular uptake of HDL lipid without protein degradation), or uptake of holo-HDL particles. An authentic HDL receptor, scavenger receptor BI (SR-BI), is highly expressed in the liver and steroidogenic tissues, where it mediates the selective uptake of HDL lipids.