Primary biliary cirrhosis and primary sclerosing cholangitis are the most common chronic cholestatic liver diseases in adults that lead to biliary cirrhosis and its inherent complications such as portal hypertension and liver failure. Although important advances in the understanding of the pathogenesis of these conditions have been accomplished in the last two decades, much work is needed to uncover the interaction of genetic and immunologic mechanisms involved in their pathogenesis. Ursodeoxycholic acid at dosage of 13 to 15 mg/kg/d is the only agent that can currently be recommended in the treatment of PBC. No medical therapy aimed at disrupting disease progression is available for patients with primary sclerosing cholangitis, although several agents with different properties are currently under evaluation. Liver transplantation is the treatment of choice for patients with primary biliary cirrhosis and primary sclerosing cholangitis with end-stage liver disease.