The hepatitis C virus (HCV) is recognized as the leading cause for parenterally transmitted hepatitis. It is characterized by a high propensity to chronicity. Several efforts have been directed towards understanding the natural history of chronic HCV infection and the immunopathogenic pathways involved in mediating liver injury in the non-immunosuppressed and immunosuppressed states. In the non-immunosuppressed setting, liver damage seems to be largely immune mediated. In contrast, in the non-immunosuppressed state, there are several other factors that may modify the natural course of the infection and play a role in mediating liver injury. In this review we will address the natural history, virological and immunological aspects of HCV infection. Also, the role played by immunosuppression and organ transplantation in modifying the course of the infection and the pathogenesis of liver injury will be discussed.