Nucleosidic reverse transcriptase inhibitors were the first class of drugs to be used for the treatment of HIV disease. Recent data on the complex pathways allowing the virus to adapt to the drugs will lead to better management of the phenomena, Similarly, better understanding of the mechanism of their toxicity will allow safer use. As these drugs are simple to use, and have a sustained effect over time with reasonable tolerance, nucleosidic reverse transcriptase inhibitors are currently the main contributors to multi-drug anti-HIV regimens. Reverse transcriptase inhibitors are currently the main contributors in multi-drug anti-HIV regimens.