Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease of uncertain etiology characterized by the destruction of the intrahepatic and/or extrahepatic ducts through inflammation and fibrosis. This ultimately leads to biliary complications including cirrhosis, cholangiocarcinoma, and eventually death. Given the uncertainty surrounding the pathogenesis of the disease, a number of different medical therapies have been studied in the treatment of PSC. However, there currently are no effective medical therapies known to halt the progression of disease. The only definitive therapy for PSC is liver transplantation. This review will primarily focus on the medical approaches that have been studied for the treatment of PSC as well as on the management of symptoms commonly associated with the disease.