Many hepatobiliary diseases can result in cholestasis. The main causes of chronic cholestasis in adults are primary biliary cirrhosis, which is characterized by portal triad inflammation and segmental necrosis of interlobular bile ducts, and primary sclerosing cholangitis, in which the intra and/or extrahepatic bile ducts undergo inflammation and fibrosis. The diagnosis is based on the presence of evidence of cholestasis and of symptoms specific for each condition. A number of drugs, sarcoidosis, total parenteral nutrition, chronic liver transplant rejection, and graft-versus-host disease can also cause chronic cholestasis. The treatment of these conditions has benefited greatly from rational use of ursodeoxycholic acid.