Recently, considerable progress has been made in understanding the molecular basis of lipoprotein metabolism, including the role of peroxisome proliferator-activated receptor (PPAR)-alpha--the specific transcription factor which, when activated, influences the expression of genes encoding for proteins involved in high-density lipoprotein (HDL) metabolism. Because the fibrates have a direct effect on PPAR-alpha and, in turn, on 5 key genes that determine lipoprotein structure and function, they are able to exert a multiple influence on HDL metabolism. Increased HDL synthesis, accelerated efflux of cholesterol, and its hepatic uptake are the ultimate outcome of fibrate influence, with a consequent enhancement of the protective effect of HDL cholesterol.