Despite progress in the use of antiretroviral drugs, mother-to-child transmission of HIV still remains a serious medical problem in resource-poor areas. There is a need to find the best method for drug delivery to reduce transmission, while keeping the risk of selection for drug-resistant viral variants low. Even when infection is prevented during pregnancy, the risk of acquiring infection by breast feeding remains significant and in some settings, is unavoidable. The ability of antiretroviral drugs or vaccines to limit transmission by breast milk is unknown. HIV vaccines are still in an early phase of development and have not yet been tested in newborns, in part due to concerns about potential of low immunogenicity due to transplacental transfer of maternal antibodies. Alternative strategies have been proposed to limit transmission using passive prophylaxis by human monoclonal antibody, but to insure product safety, trials have been slowed. Due to such concerns, animal models may provide an alternative for testing efficacy in human newborns. In this review, advances made using such models will be compared for mother-to-child transmission of lentivirus with that of HIV-1. In addition, some perspectives on integrating the data obtained from these models as a groundwork for future clinical work will be presented.