Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown origin characterized by progressive inflammation, destruction, and fibrosis of the intrahepatic and extrahepatic bile ducts. The disease leads to obliteration of intrahepatic bile ducts and to biliary cirrhosis, end-stage liver disease, and portal hypertension. Primary sclerosing cholangitis commonly occurs in the presence of inflammatory bowel disease. Its exact etiology remains unknown. As a result, there is no existing effective medical management to delay or modify the progression of the disease. Ursodeoxycholic acid, the most well-studied drug for primary sclerosing cholangitis, has demonstrated promising results when used in combination with an immunosuppressant or antibiotic. To date, liver transplantation remains the only confirmed long-term treatment of primary sclerosing cholangitis, which now accounts for 6% of adult and 1% of pediatric liver transplantations in the United States. Primary sclerosing cholangitis represents an important liver disease with major morbidity and mortality.