Hepatitis C remains a global epidemic. Approximately 3 % of the world's population suffers from chronic hepatitis C, which is caused by hepatitis C virus (HCV)-a positive sense, single-stranded RNA virus of the Flaviviridae family. HCV has a high propensity for establishing a chronic infection. If untreated chronic HCV carriers can develop severe liver disease including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Antiviral treatment is only partially effective, costly, and poorly tolerated. A prophylactic or therapeutic vaccine for HCV does not exist. Mechanistic studies of virus-host interactions, HCV immunity, and pathogenesis as well as the development of more effective therapies have been hampered by the lack of a suitable small animal model. Besides humans, chimpanzees are the only species that is naturally susceptible to HCV infection. While experimentation in these large primates has yielded valuable insights, ethical considerations, limited availability, genetic heterogeneity, and cost limit their utility. In search for more tractable small animal models, numerous experimental approaches have been taken to recapitulate parts of the viral life cycle and/or aspects of viral pathogenesis that will be discussed in this review. Exciting new models and improvements in established models hold promise to further elucidate our understanding of chronic HCV infection.