Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates the management of patients infected with human immunodeficiency virus (HIV), increases medical costs, alters the prescription patterns, and affects the guideline recommendations. Among the clinical consequences derived from HAART-related liver toxicity, hypersensitivity reactions and lactic acidosis are recognized as acute events with potential to evolve into fatal cases, whereas there seems to be other syndromes not as well characterized but of equal concern as possible long-term liver complications. Belonging to the latter category of syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal hypertension, and nodular regenerative hyperplasia are discussed in this review. Updated information on liver toxicity of current antiretroviral drugs, including the most recently licensed, is provided. Management and prevention of liver toxicity among HIV-infected patients treated with HAART are reviewed as well. (HEPATOLOGY 2010;52:1143-1155) P hysicians treating human immunodeficiency virus (HIV)-infected patients often deal with aminotransferase elevations which have to be interpreted and managed. New hepatic problems which might be related to the use of highly active antiretroviral therapy (HAART) continue to be revealed. In addition, new antiretrovirals have been licensed for which information on liver safety is limited. I refer to past reviews for previous information on the subject. [1][2][3][4][5][6][7][8] After those publications, prescription patterns and guideline recommendations have continued to evolve, and physicians treating HIV in 2010 manage new antiretroviral drugs and new aspects of the epidemics. 9 This review focuses on the clinical consequences of liver toxicity associated with HAART, updates information on the subject, and includes liver safety data of most recently approved antiretroviral drugs. This article aims to help health care providers prevent and handle antiretroviral toxicity within contemporary management of patients with HIV.