This review covers the various aspects of the immune system that allows the relationship between the hepatitis-C virus, the host and chronic low-level inflammation, to be highly flexible and able to defend the host from persistent infections. This ambiguity mainly stems from the property of the immune system that can be both protective and harmful. Immunity cannot be fully protective without producing a certain degree of damage (acute hepatitis resulting in resolving HCV infection). In addition, the balance between protection and tissue damage is critical for the development of chronic HCV infection. The establishment of a state of chronic low-level inflammation is instrumental to limit liver immunopathology, to limit viral spread, and ultimately to ensure a long-lasting survival of the host. It is dictated by a fine equilibrium maintained by multiple immunologic mechanisms, including: sensory perception of innate immunity, virus-specific T and B cell functions, control of immune responses, and finally the balance between immunity and immunopathology that has principally evolved to favor the species survival.