Antiretroviral therapy is not uncommonly associated with drug toxicities, and hepatotoxicity occurs in approximately 20% of individuals prescribed antiretroviral therapy. Mitochondrial toxicity causing lactic acidosis is a rare but fatal complication that has been described in some HIV-infected patients treated with nucleoside analogue reverse transcriptase inhibitors. In this report, we describe the course of an HIV-infected patient receiving antiretroviral therapy who developed lactic acidosis after liver transplantation for HCV-induced liver disease.