The coinfection of HIV and HCV has become a pathology with several distinctive characteristics. Pathogenesis of liver damage in patients with HIV and HCV coinfection is complex and multifactorial. It derives from a balance of factors which interact among themseles in a dynamic way. The reasons for the accelerate course of HIV/HCV coinfection are mainly related to two principal causes: the persistence of HCV, which depends upon alterations of cell-mediated immunity, and the activation of the immune system towards secretion of proinflammatory and profibrotic cytokines. This review will first focus on the characteristics of both these immune-mediated mechanisms, and then their implication on fibrogenesis as well as on other pathogenetic mechanisms, such as interactions between viruses and the deficit of protective mechanisms. A better knowledge of adaptive immune mechanisms, cytokine alteration, interference with host defense mechanisms, and the "cross-talk" among the viruses will improve the understanding of the pathogenetic mechanism and provide the opportunity to cure this disease.