The debate over how to best guide HIV-infected mothers in resource-poor settings on infant feeding is more than two decades old. Globally, breastfeeding is responsible for approximately 300,000 HIV infections per year, while at the same time, UNICEF estimates that not breastfeeding (formula feeding with contaminated water) is responsible for 1.5 million child deaths per year. The largest burden of these infections and deaths occur in Sub-Saharan Africa. Using this region as an example of the burden faced more generally in other resource-poor settings, we contrast the evolution of the clinical standard of care for infant feeding with HIV-infected mothers in high-income countries to the current international clinical guidelines for HIV-infected mothers and infant feeding in resource-poor settings. While the international guidelines of exclusive breastfeeding for a 6-month period seem to offer the least-worst strategy for reducing mother-to-child transmission of HIV during infancy while conferring some immunity through breastfeeding post-6 months, we argue that the impact of the policy on mothers and healthcare workers on the ground is not well understood. The harm reduction approach on the level of health policy translates into a complicated, painful moral dilemma for HIV-positive mothers and those offering them guidance on infant feeding. We argue that the underlying socio-economic disparities that continue to fuel the need for a harm reduction policy on infant feeding and the harm to women and children justify: (1) that higher priority be given to solving the infant feeding dilemma with improved data on safe feeding alternatives, and (2) support of innovative, community-driven solutions that address the particular economic and cultural challenges that continue to result in HIV-transmission to children within these communities. © Springer Science+Business Media B.V. 2008.