Feeding nine billion people with environmentally sustainable agricultural production systems delivering nutritious food is a challenge. Research bridging the biophysical and social sciences will be critical as the solutions to this challenge will require attention to the systems in which component technologies and innovations are brought to bear.  As we conceptualize these issues, we will  not only examine the interactions of water, soil, climate, weather, and the biota in the ecosystem, but also the socio-cultural, political and economic systems that overlay and interact with the biophysical. The Feed the Future Research Strategy advances this thinking with a focus on target agro-ecologies in the developing world. To advance smallholder productivity and production, we will work with our research partners to develop relevant component technologies, innovations, and approaches to advance productivity and transform production systems, while conserving the natural resource base, reducing smallholder farmer risk, and integrating human nutrition and health goals throughout the food system. Selected agro-ecologies will be the primary targets of the Feed the Future research strategy and will complement research being conducted in other important agricultural areas. The agro-ecologies that will be emphasized are: Sudano-Sahelian agro-pastoralist system in West Africa, East African highlands systems, East and Southern African maize-based system in multiple countries, and the cereal-based systems of South Asia. This eco-regional approach will enable more targeted attention to research questions of direct relevance to specific farming systems in particular social, policy and economic contexts. It will require global public goods type research as well as more focused regional/country-specific research to provide the necessary innovations and technologies that will drive inclusive agriculture-led economic growth thereby ensuring that smallholder farmers benefit from FTF research efforts.