Hepatitis C is among the most common causes of chronic liver disease affecting approximately 1% of the world's population. End-stage hepatitis C virus (HCV)-related chronic liver disease is the leading indication for orthotopic liver transplantation worldwide. Despite these facts, many questions regarding the natural history of HCV infection remain unanswered. Is progression to end-stage liver disease inevitable? Over what time period does it occur? If progression is not inevitable, can we identify those persons destined to have end-stage liver disease and possibly prevent or slow progression?