End-stage liver disease due to hepatitis C virus infection (HCV) is the principal indication for liver transplantation. In the USA, over a third of available liver allografts are transplanted into recipients with chronic HCV infection. Reinfection of the graft is universal, but the impact of reinfection on short- and long-term liver function is highly variable. HCV infection in liver transplantation recipients is characterized by an accelerated fibrogenesis, with approximately a third of patients developing cirrhosis within 5 years of follow-up. HCV is associated with decreased patient and graft survival when compared with other indications of orthotopic liver transplantation. The mechanisms responsible for the accelerated liver damage in HCV-infected orthotopic liver transplantation recipients remain largely unknown.