Worldwide, the AIDS pandemic continues almost relentlessly. Women are now representing the fastest growing group of newly infected HIV-1 infected patients. The risk of mother-to-child-transmission (MTCT) of HIV-1 increases proportionally as many of these women are of childbearing age. The screening of pregnant women, the early diagnosis of HIV-1 infection, and the administration of antiretroviral therapy (ART) have helped to reduce MTCT significantly. However, this holds true only for developed countries. In many resource-poor countries, access to ART is limited, and breastfeeding, a major route of HIV-1 transmission, is essential to protect the infant from other infectious diseases preponderant in those geographic regions. HIV-1 infected children, in contrast to adult patients, have higher levels of virus replication that decline only slowly, and a subset progresses to AIDS within the first two years. Thus, it is imperative to understand pediatric HIV-1 pathogenesis to design effective prevention strategies and/or a successful pediatric HIV-1 vaccine. The review summarizes how MTCT of HIV-1 in humans can be modeled in the infant macaque model of SIV infection. Importantly, the infant macaque model of SIV infection provides the opportunity to study early virus-host interactions in multiple anatomic compartments. Furthermore, the review underlines the importance of evaluating SIV/HIV immune responses in the context of the normal developmental changes the immune system undergoes in the newborn. Thus, the pediatric SIV infection model provides a unique resource for preclinical studies of novel intervention therapies and vaccine strategies to stop MTCT of HIV-1.