Liver disease is an important complication of human immunodeficiency virus (HIV) infection. As HIV-infected patients live longer, they develop long-term manifestations of chronic HIV infection and/or treatment complications. Progressive liver disease is one of the leading causes of morbidity and mortality in this patient group. Underlying hepatitis B and/or C virus infection is extremely common. All classes of antiretroviral drugs have been associated with some hepatotoxicity, and patients often receive other potentially liver-damaging drugs. Alcohol use is common and frequently underestimated. All of these issues make liver disease an important factor in making antiretroviral decisions. Clinicians should weigh underlying disease, behavioral issues such as drugs and alcohol, and concomitant therapy when choosing antiretrovirals in such patients. We need more research in this area, especially with regard to mechanisms, risks, and management - for specific drugs and regimens - to ensure that our patients receive the benefits of antiretroviral therapy in the safest manner possible.