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Primary sclerosing cholangitis (PSC) is a rare cholestatic disorder of the liver, with strictures in the bile ducts leading to cirrhosis of the liver in a proportion of patients. PSC is commonly associated with inflammatory bowel disease and increased risk of cholangiocarcinoma, gall bladder cancer, colorectal cancer, and hepatocellular carcinoma. Medical therapies are primarily aimed at symptom management and disease-modifying therapies are limited. Endoscopic therapies are used in patients with dominant strictures and liver transplantation is a last resort. In this article, the authors aim to comprehensively review the epidemiology, diagnosis, and management of PSC with emphasis on risk of malignancies and management of PSC. The authors also survey the advances in pathogenesis understanding and novel medical therapies for PSC.