This review highlights recent developments in the molecular pathogenesis of cholestasis as well new aspects of pathogenesis and management of clinical cholestatic disorders.Highlights include the role of nuclear receptors including FXR ligands as potential therapeutic agents, new genetic defects for pediatric cholestasis and sclerosing cholangitis, and novel infections and environmental agents as etiologies for primary biliary cirrhosis. Important clinical studies have been published in the area of pediatric cholestatic syndromes, intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, primary and secondary sclerosing cholangitis, cholestasis of sepsis, viral cholestatic syndromes, and drug-induced cholestasis.These advances continue to improve understanding of the pathophysiology, diagnosis, and management of cholestatic liver disease.