The global epidemiology of HIV/AIDS is rapidly evolving in low and middle income countries. Women and adolescent females in Sub-Saharan Africa are at risk of HIV acquisition due to a myriad of complex biological, behavioral and structural factors. Primary HIV infection among women primarily drives the pediatric HIV epidemic. Postnatal transmission of HIV during breastfeeding is a major concern in LMIC, particularly in Sub-Saharan Africa where breastfeeding remains the only feasible, safe and culturally acceptable infant feeding choice. Given the remarkable discoveries in biomedical interventions to prevent sexual transmission of HIV and MTCT during breastfeeding, there is now a unique opportunity to rapidly implement combination HIV prevention packages, provide quality prevention of mother-to-child HIV transmission services, and improve maternal and infant survival. Although rapid scale-up of PMTCT interventions has occurred in Sub-Saharan Africa in the past five years, significant challenges remain towards reaching the ambitious goal of virtual elimination of new HIV infections among children on a global scale by 2015 and keeping their mothers alive. Rapid translation of scientific discoveries into policy and practice in conjunction with strong commitment from national leadership and global partners is crucial to end the pediatric AIDS and achieve a HIV-free generation.