Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic disease characterized by hepatic inflammation and obliterative fibrosis, resulting in both intra- and extra-hepatic bile duct strictures. End-stage liver disease and bile duct carcinoma represent frequent complications. Incidence and prevalence of PSC in USA have been recently estimated as 0.9 per 100,000 person-years, and 1-6 per 100,000 person-years, respectively. Major diagnostic criteria include the presence of multifocal strictures, beadings of bile ducts, and compatible biochemical profile, once excluded secondary causes of cholangitis. Since the aetiology of PSC remains poorly defined, medical therapy is currently limited to symptom improvement and prolonged survival. Ursodeoxycholic acid (UDCA), corticosteroids and immunosuppressants have been proposed alone or in combination to improve the clinical outcome. In selected cases, surgical or endoscopic procedures need to be considered. Orthotopic liver transplantation (OLT) is at the moment the only definitive approach although disease relapse has been reported. In this article the state of the art in PSC treatment and future promises in this field are reviewed.