Summary: Encouraging efficacy data have been obtained in the hepatitis C virus (HCV) chimpanzee model using prophylactic vaccines comprising adjuvanted recombinant envelope gpE1/gpE2 glycoproteins or prime/boost immunization regimens using defective adenoviruses and plasmid DNA expressing non-structural genes. While usually not resulting in sterilizing immunity after experimental challenge, the progression to chronic, persistent infection (which is responsible for HCV-associated pathogenicity in human) is inhibited. These and other vaccine candidates are in clinical development for both prophylactic as well as possible therapeutic applications. Given that other vaccines tested in the chimpanzee model may be possibly increasing the rate of chronicity, it is very important that this model continues to be available and used prior to initiation of clinical development. Several vaccine monotherapy trials in chronically infected HCV patients are resulting in small declines in viral load, suggesting that in future, combining vaccination with antiviral drug treatment may be beneficial.