The HIV pandemic continues to levy a heavy burden on the human race world-wide. The estimated number of people who became newly infected with HIV in 2009 was 2.6 million; most of these individuals live in Sub-Saharan Africa, followed by India and Southeast Asia. An estimated 370,000 new cases of pediatric infections occurred globally in 2009 (or more than 1,000 new infections every day), practically all of them through mother-to-child transmission. Up to 40% of all new infant HIV infections occur during breastfeeding. While breastfeeding by HIV-infected mothers is not recommended in the U.S. and other resource-rich settings where safe replacement feeding is easily available, the situation is different in many resource-limited settings, where replacement feeding is not safe or available and carries a high risk of infections (diarrhea, pneumonia) and infant malnutrition. Mothers in such settings are faced with a difficult dilemma: to breastfeed their infants in order to provide their infants with its many benefits (nutritional, immunologic, cognitive), but to also risk transmitting HIV. These challenges have prompted an intensive search for new prophylactic and therapeutic strategies in order to prevent infants from acquiring HIV infection through breastfeeding.