Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology, characterized by fibrosis and inflammation of the intra- and extrahepatic bile ducts. PSC is usually seen in association with inflammatory bowel disease, particularly in younger patients with extensive ulcerative colitis. Crohn's disease is seen in more than 10% of all patients with PSC. The bowel disease may produce no symptoms in some patients, and the clinical course is usually silent. The development and widespread use of endoscopic retrograde cholangiopancreaticography (ERCP) have enabled us to diagnose the disease far more often than was possible only a decade ago, and also to recognize that PSC has a much wider clinical and pathologic spectrum than previously realized. Most patients with concomitant ulcerative colitis and persistently abnormal liver function tests are likely to have PSC. Patients with PSC usually have a cholestatic biochemical profile, whereas the histologic features of the liver biopsy are variable and often nonspecific. Cholangiography displaying strictures and beading is diagnostic of the disease. The prognosis is variable, with a benign clinical course in many patients. However, an increased rate of cholangiocarcinoma is found in PSC, as is an increased rate of colonic cancer in patients with PSC and ulcerative colitis.