Chronic liver diseases caused by either hepatitis B or C viruses are a major health problem around the world. Despite major advances accomplished in recent years in understanding the physiology of both viruses using in vitro and/or in vivomodels, there is no vaccine for HCV available. Moreover, susceptibility to acute and chronic infection and the response to treatments are different between HBV or HCV infected patients. Crucial information can be collected using a robust cell model that permits the culture of clinical isolates along with the investigation of the virus-host interaction. The recent progress in the field of cell reprogramming and differentiation has opened new opportunities in viral hepatitis research raising the hopes of developing new improved therapeutics. In this review, we discuss current models for hepatitis B and C studies and their limitations, and also the iPSC model, and its relevance to the viral host cell interactions.