In the last few years, the interactions between mitochondria and infection with the human immunodeficiency virus (HIV) have received careful attention. Starting from the first studies regarding the presence of mitochondrial damage in cardiac tissue from patients who died of AIDS, researchers have investigated different aspects of the interactions between the virus and mitochondria, from acute primary infection to the final stages of the disease. Only recently a significant impulse to this type of research has come from the observation that the so called "highly active antiretroviral therapy" (HAART), a combination of potent antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors, is capable of damaging these organelles and cause a clinical syndrome called lipodystrophy. There is still an open debate concerning the exact responsibility of HAART as well as on metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. The hypothesis that drug-induced damage to mitochondrial (mt) DNA is able to alter mitochondria functionality to a similar extent as that occurring in genetic disease affecting mtDNA suggests that mitochondria plays a crucial role in the pathogenesis of this syndrome. In this paper, data concerning the interactions between mitochondria and HIV infection will be reviewed.