End-stage liver disease caused by the hepatitis C virus (HCV) is a major indication for liver transplantation. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 75-90% of patients, and 5-30% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by the side-effects of antiviral drugs. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25-35% of patients, but indications, modality and duration of treatment should be assessed.