Human immunodeficiency virus (HIV) infection and the pharmacological treatment thereof have both been shown to affect mitochondrial function in a number of tissues, and each may cause specific organ pathology through specific mitochondrial pathways. HIV has been shown to kill various tissue cells by activation of mitochondrial apoptosis. Nucleoside analogues, used extensively to treat HIV infection, are known to influence a number of steps affecting mitochondrial DNA integrity. This review describes the basic physiology, pharmacology and pathophysiology of HIV infection and the nucleoside analogues regarding mitochondrial function and discusses the progress made in this field with respect to the measurement of these effects and the prediction of potential drug toxicity.Keywords: highly active antiretroviral treatment, HIV, nucleoside reverse transcriptase inhibitor, mitochondrial DNA, mitochondrial toxicit