A combination of three or more antiretroviral drugs, commonly called 'highly active antiretroviral therapy' (HAART), has become the standard-of-care treatment for HIV-infected patients in the developed world. There are now 21 licensed anti-HIV drugs to choose from when starting a HAART regimen. The currently approved antiretroviral drugs fall into four categories: nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and fusion inhibitors. Novel compounds currently in preclinical or clinical development are either focusing on new viral proteins or the same specific viral elements targeted by the available drugs. When developing new anti-HIV drugs of an already existing class, focus should be held on maximising potency, minimising toxicity, diminishing the risk for resistance development and producing effective drugs for patients who already have resistance to currently available drugs. In addition, pill burden should be ideally reduced to once-daily dosing, thereby enhancing a patient's adherence and reducing treatment costs. The present review focuses on emerging drugs to inhibit the reverse transcriptase of HIV.