Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that progresses to death as a result of liver failure or cholangiocarcinoma. Susceptibility to PSC is associated with the HLA A1-B8-DR3 haplotype, and new associations with HLA C and tumor necrosis factor genes have been detected. A circulating antineutrophil cytoplasmic antibody is found in many patients with PSC, but its antigen or antigens have not been identified. Some studies suggest that this antigen may be an anti-nuclear membrane protein rather than cytoplasmic. Diagnosis of PSC is based on endoscopic retrograde cholangiography, but magnetic resonance cholangiography is a promising noninvasive alternative. Medical treatment remains elusive. In highly selected patients, endoscopic or even surgical treatment can be tried. Orthotopic liver transplantation remains the only effective therapy, but inflammatory bowel disease may run a more aggressive clinical course after this procedure. Sclerosing cholangitis may recur after transplantation, but this has had no clinical implications to date.