Administration of potent antiretroviral combination therapy in the second and third trimester of pregnancy and during delivery, and for 6 weeks postpartum to the infant, may reduce HIV transmission from the mother to the child to <2% in formula-fed infants. In resource-constrained settings where women have limited access to antenatal care, use of shorter and more practical regimens, including nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs) commenced later in pregnancy, has demonstrated efficacies ranging from 18% to 70% in breast- and bottle-fed populations. Because shorter interventions include regimens such as single-dose nevirapine or zidovudine monotherapy, which do not provide maximal suppression of viral replication, emergence of resistant mutations in mother and infant occurs frequently, primarily after exposure to drugs with low genetic barriers (i.e. those requiring only one genotypic mutation to develop resistance), such as nevirapine. Different studies have reported nevirapine resistance rates ranging from 25% to 69% in mothers receiving single-dose nevirapine alone. Because NNRTI-based combinations of antiretroviral agents are recommended as first-line therapy in countries where single-dose nevirapine is the main option for preventing mother-to-child transmission of HIV, concerns have been raised as to whether single-dose nevirapine prophylaxis can compromise the efficacy of subsequent NNRTI-based antiretroviral therapy regimens. However, although some studies have shown that nevirapine exposure may impact on short-term virological outcome, the clinical relevance of nevirapine resistance remains unclear, especially in women who start treatment >6 months after delivery or in those who are not severely immunocompromised. Furthermore, studies have shown that adding short-course (up to 7 days) zidovudine or zidovudine/lamivudine prophylaxis after delivery may dramatically reduce the occurrence of nevirapine resistance in both mothers and infants. Until data are available that allow a better understanding of the relevance of antiretroviral drug resistance acquired as a result of mother-to-child HIV transmission prophylaxis, women and children who have previously received single- dose nevirapine as part of a mother-to-child transmission prevention strategy should be considered eligible for NNRTI-based regimens and should not be denied access to antiretroviral therapy.