OBJECTIVE Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree complicated by cirrhosis and cholangiocarcinoma. It is immune mediated, although the precise aetiology remains unknown. RESULTS The research into aetiology, genetic associations, pathogenesis, epidemiology, diagnosis of cholangiocarcinoma and medical treatments are discussed. CONCLUSIONS Multiple gene polymorphisms and human leucocyte antigen haplotype associations with primary sclerosing cholangitis have been investigated. Common inflammatory bowel disease associated polymorphisms and ulcerative colitis associated human leucocyte antigen haplotypes are not associated with primary sclerosing cholangitis. Biliary epithelial cells may mediate their own destruction by exaggerating innate and adaptive immune responses to bacterial products in the liver. The natural history of large and small duct primary sclerosing cholangitis has been reviewed. Positron emission tomography may be a useful adjunct to current imaging modalities in the pretransplant assessment of patients to exclude cholangiocarcinoma. Ursodeoxycholic acid remains the most studied medical treatment for primary sclerosing cholangitis; pilot studies suggest a possible role for tacrolimus and silymarin, however further studies are required.