Hepatitis C virus (HCV) is a major cause of chronic liver disease. About 170 million people worldwide are chronically infected. No preventive or therapeutic vaccine is available. Current antiviral combinations based on pegylated interferon alpha (IFN-alpha) and ribavirin have limited efficacy, poor tolerability and high cost. End-stage liver disease due to chronic HCV infection is a leading indication for liver transplantation (LT). However, re-infection of the liver graft is inevitable, with a high risk of cirrhosis within 5 years. To infect the graft, circulating virions need to attach to and enter hepatocytes, via viral envelope glycoproteins E1-E2. E1-E2 can react with cell receptors despite the presence of neutralizing antibodies. [corrected] A better understanding of the early steps of viral attachment and escape from neutralizing antibodies could lead to novel antiviral strategies.