The non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important group ofantiretroviral drugs in the treatment of a chronic HIV-I infection. The risk of viral resistance to NNRTIs is strongly diminished when they are used as part of a highly active antiretroviral combination therapy (HAART). Randomised trials have shown that nevirapine and efavirenz have a comparable antiretroviral efficacy. While rash and hepatotoxicity are associated with the use of nevirapine, the use of efavirenz is associated with neuropsychiatric abnormalities. The increase in HDL-cholesterol, which may be associated with a lower risk of cardiovascular disease, is greater with nevirapine than with efavirenz. The choice between the two drugs can be tailored to the needs of the patient. The rapid selection ofNNRTI-resistant HIV-I strains during the sub-optimal use of nevirapine and efavirenz demands the development of new NNRTIs.