Patients with PSC should be viewed as having a disease that frequently progresses to liver failure if followed long enough. The rate of disease progression is variable and can occur without changes in symptoms or signs. With the advent of ERCP and widespread use of liver tests on routine examinations, the diagnosis of PSC is being made earlier and survival estimates have lengthened. Varying methods of survival analysis have also been responsible for differing opinions regarding the natural history of this disease. Nevertheless, it is probable that with close prospective, long-term follow-up, evidence of disease progression and increased mortality becomes apparent. Challenges for the future include being able to predict accurately the rate of disease progression and timing of liver failure in the individual patient. Preliminary studies using statistical survival modeling have been developed; however, further refinement of these models will be needed prior to application to clinical trials and liver transplantation.