Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by a progressive obliterating fibrosis of the intrahepatic and extrahepatic bile ducts. The pathogenesis of PSC is poorly understood but it is thought to be an immune-mediated disease. The optimal therapy which successfully improves symptoms, delays progression towards liver failure and transplantation and prevents the onset of cholangiocarcinoma remains elusive. Although current treatments are used to manage cholestasis and its consequences and some of the more general complications of the disease, none of the current therapeutic agents have been shown to retard and reverse the rate of disease progression. The role of cupruretics, corticosteroids, methotrexate, antifibrogenic agents and ursodeoxycholic acid in the treatment of PSC is reviewed. Orthotopic liver transplantation remains the only therapeutic option for advanced PSC but the timing of transplantation remains controversial and the possibility of recurrence of the disease in the graft is increasingly recognised. It is likely that greater insight into the pathogenetic mechanisms involved in PSC will allow therapy to be targetted more specifically at the biliary epithelium.