The use of antiretroviral drug therapies in HIV-1 infected pregnant women and their infants has resulted in significant reductions in the rates of mother-to-child transmission of HIV-1. A number of drugs that target the reverse transcriptase enzyme have been tested either alone or in combination in short-course regimens tailored for use in developing countries. The drug of choice is nevirapine, which is cheap, easy to administer and highly effective even following a single dose to mother and child. However, this regimen is associated with the selection of mutations associated with drug resistance. While these mutations do not compromise the ability of nevirapine to prevent mother-to-child transmission there is some concern that they may compromise future treatment options. Here we review the current data on HIV-1 drug resistance mutations and what they might mean in terms of efficacy of antiretroviral therapies to prevent mother-to-child transmission.