Animal models for the study of HCV

•Ethical restraints on the use of chimpanzees have opened a quest for alternative animal models to study HCV.•Mice require humanization of the liver to become susceptible to HCV infection.•Alternatively the virus can be adapted to the mouse environment.•Immunocompetent mice with (genetically) humanized liver are available but entail further optimization.•Recently identified non-primate hepaciviruses may provide novel surrogate animal models.