The review considers the design of antiretroviral drugs based on nucleoside analogs. Approximately 30 drugs have been approved for treating HIV-infected patients over the past 25 years. Seven nucleoside drugs act as HIV reverse transcriptase (RT) inhibitors and are clinically used in combination with inhibitors of other viral enzymes, integrase and protease, and nonnucleoside inhibitors of HIV RT. Toxicity of nucleoside drugs and the possibility to obtain safe anti-HIV drugs by constructing their depot forms are discussed. The results of developing anti-HIV drugs in Russia are described. The future prospects of anti-HIV research are considered.