Primary sclerosing cholangitis in children can mimic autoimmune hepatitis in the absence of inflammatory bowel disease. Most adult patients have been identified with human leukocyte antigens that either predispose or protect against disease. Novel class I alleles and cytokine polymorphisms may also contribute to disease susceptibility. Primary alpha-hemolytic streptococci infection does not appear to directly cause primary sclerosing cholangitis. Promising diagnostic modalities such as single photon emission tomography require further study in comparison with cholangiographic techniques. Positron-emission tomography and DNA cytometry appear promising for confirming occult cholangiocarcinoma when present. The chemoprevention effects of ursodeoxycholic acid on colorectal dysplasia await further investigation. Initial results from high-dose ursodeoxycholic acid in halting disease progression, however, suggest a beneficial effect. In contrast, the impact of endoscopic therapy on natural history remains unresolved. Although liver transplantation continues to be effective for end-stage liver disease, disease recurrence in the allograft is a controversial topic.