Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder that most commonly affects middle-aged men. PSC is strongly associated with IBD, and in this setting the risk of colorectal cancer is markedly increased. Cholangiocarcinoma, and its devastating consequences, is another well-recognized complication of PSC. This condition tends to progress to end-stage liver disease, and patients with PSC have reduced survival rates compared with the general population. Despite significant research efforts in this field, the pathogenetic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. Effective medical therapy is lacking; liver transplantation is the only curative treatment modality, with excellent outcomes in this patient population.