PSC is the most common and most important hepatobiliary disease seen in association with IBD. Approximately 5% of all patients with CUC have PSC, and most patients with PSC ultimately develop IBD, usually CUC. PSC and CUC appear to be associated diseases-one does not cause the other, but common pathogenic mechanisms are likely involved. PSC alone does not differ from PSC with IBD with regard to clinical, biochemical, cholangiographic, and hepatic histologic features. There is an overlap syndrome of CAH and PSC in patients with CUC suggesting that patients with CAH and CUC should have a cholangiogram. Colectomy in patients with PSC and CUC does not influence the PSC and, if done for colitic indications, should be accompanied by an ileal pouch-anal anastomosis. Serologic markers are being identified, which are frequently found in PSC with or without CUC, including markers for the dreaded complication of cholangiocarcinoma. Unfortunately, patients with PSC and CUC are doubly at risk for malignancies of the colon and biliary system. Medical therapies are being assessed that may beneficially affect both PSC and CUC, and liver transplantation is life-saving for patients with advanced PSC. Although CAH and gallstones are also found in association with IBD, they are much less common and of considerably less clinical importance than PSC associated with IBD.