Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease caused by progressive inflammatory destruction of intrahepatic and extrahepatic bile ducts, and ultimately cirrhosis. PSC occurs primarily in patients with underlying ulcerative colitis and affects primarily young to middle-aged men. PSC is believed to be an autoimmune disease mediated by immune dysregulation in patients with genetic susceptibility. One possible mechanism for the development of PSC is the homing of memory lymphocytes to the biliary tract. Cholangiography is the gold standard for diagnosis of PSC. The typical radiologic findings include multifocal strictures and dilation involving the intrahepatic or extrahepatic biliary tract, or both. Although no medical therapy has proved beneficial, a variety of agents have been tested, some of which appear promising and deserve further study. Highdose ursodeoxycholic acid may have benefit in slowing disease progression; a multicenter placebo-controlled trial is ongoing. Liver transplantation is a good option for patients with advanced PSC, although the disease can recur after successful transplantation.