HIV and HCV share transmission routes and, for this reason, 25% of HIV patients are also infected by HCV, and up to 80% of HIV-positive iv drug users. AIDS incidence and mortality are not higher in HCV positive patients, but liver morbidity and mortality are increased. Spontaneous clearance of HCV after infection is less frequent among HIV positive patients. Liver fibrosis progresses faster in HIV-HCV co-infected patients compared to HCV mono-infected, but this can be partially slowed down with effective antiretroviral therapy and immune restoration. Response to HCV treatment is also weaker among co-infected patients. Pharmacological interactions and increased toxicity of antiretroviral drugs and anti-HCV drugs are challenging for clinicians, especially if the recently approved anti-HCV proteases are used.