Reciprocal interactions between Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) are characterized by the absence of clear impact of HCV on HIV; by contrast, HIV markedly modified the natural history of HCV (high viral load, more severe liver disease) at least before the introduction of highly active antiretroviral therapies (HAART). HAART has completely modified the pattern of hepatic events in HIV infection and the liver disease is one of the leading causes of morbidity and mortality nowadays, reflecting several non-exclusive pathogenic processes that include drug-related hepatotoxicities, chronic hepatitis C infection, other liver diseases such as steatosis or non-alcoholic steato-hepatitis (NASH) and other liver diseases that are common in the setting of alcohol or drug abuse. The harmful impact of HIV underlines the need for improving: