Secretion of bile salts from the hepatocyte into bile is the major driving force for the generation of bile flow. Identification of the bile salt export pump (BSEP, ABCB11) as the main adenosine-triphosphate-dependent bile salt transporter in mammalian liver has led to a greater understanding of the biliary bile salt secretory process and its regulation. The biology and pathobiology of BSEP have been the subject of many recent studies. Thus, it has been recognized that while mutations in the gene encoding BSEP are responsible for a subgroup of progressive familial cholestasis (progressive familial intrahepatic cholestasis subtype 2), a pediatric cholestatic disorder that may progress to cirrhosis, defective expression or function of BSEP may underlie some forms of drug-induced cholestasis. The present review summarizes recent data on the molecular properties and regulation of BSEP, as well as the clinical implications of absent or defective function of this hepatic efflux pump.