This issue of Hot Topics in Viral Hepatitis provides an update on the most recent findings concerning those patients with chronic hepatitis C virus (HCV) infection who are at the same time coinfected with the human immunodeficiency virus (HIV). This subgroup of chronic hepatitis C patients is of major concern, not only because they are notoriously characterized by an aggressive liver disease, with accelerated progression to the cirrhotic stage, but also because they represent the typical ‘difficult-to-treat’ HCV-infected patients poorly responding to currently available therapy. While the number of opportunistic infections among HIV patients has decreased dramatically due to the use of antiretroviral therapy, the rapid course of chronic hepatitis C in dually infected patients together with the significant hepatotoxicity of antiretroviral drugs, have allowed HCV-associated liver disease to become a major cause of morbidity and mortality among HIV-infected individuals. Many coinfected patients may now progress to the advanced liver disease stage, opening the debate about liver transplantation in this setting. Dr. Soriano and colleagues provide an up-to-date overview of the natural history of liver disease in HIV/HCV coinfection. Dr. Puoti reports on recent advances in anti-HCV therapy in chronic hepatitis C patients with HIV coinfection. Available therapy schedules, which allow curing HCV infection in about 60% of monoinfected patients, are effective in approximately 40% of cases of coinfection with HIV. Finally, Dr. Miró and colleagues conclude the monograph by addressing the sensitive issue of liver transplantation in individuals coinfected with HIV and HCV.