Significant progress has been made in preventing transmission of HIV-1 from mother to infant. With combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Abbreviated regimens covering labour and the first few days of neonatal life have shown considerable promise in the developing world. Several questions and challenges remain, however. These include choice of the optimal antiretroviral agent(s) and duration of the regimens, availability of antiretroviral agents in developing countries, long-term safety of antiretrovirals during pregnancy and early neonatal life and the problem of breastfeeding transmission in countries where alternatives to breastfeeding are not available. A wider array of strategies for prevention of mother-to-child transmission of HIV-1 during breastfeeding, including passive and active immunisation, may offer much needed answers to the problem of continued HIV transmission from mother to infant.