Recent projections suggest that the production of cereal staples in South Asia must nearly double by 2050 to ensure regional food sufficiency.  Contemporary challenges to intensified and more sustainable production of staple crops in South Asia vary significantly with geography and range from groundwater decline and overuse of inputs in areas of the Northwest Indo-Gangetic Plains (IGP), to flooding risk and low levels of private investment in the Eastern IGP, and drought in rainfed areas in the hills of Nepal and central India.  Compounding the breadth and diversity of current challenges is the emergence of new factors such as less predictable seasonal weather patterns and rapidly declining labor availability.  Catalyzing durable development at scale in S. Asia is not a simple task with millions of smallholder farmers that must be reached through approaches that not only increase grain productivity, but also reduce the risks of crop failure while improving livelihoods.   In partnership with the NARES and other stakeholders, several CG centers have been actively working towards sustainable agricultural intensification in S. Asia since the late 1980s.  Although progress has been made, steep obstacles remain that require new and more robust strategies that are explicitly geared towards achieving development goals.  With support from USAID and the Gates Foundation, a regional food security initiative called the Cereal Systems Initiative for South Asia (CSISA) was launched in 2009.  CSISA employs a novel hub-based model for participatory technology development, refinement, and dissemination.  Priority areas for CSISA investments that can decrease production costs while intensifying yields and reducing environmental externalities include conservation agriculture, site-specific nutrient management, and improved technology targeting .   CSISA also endeavors to place technologies in the context of markets, risk, knowledge diffusion pathways and other potential barriers to sustainable development that must be addressed alongside technological innovation to achieve and sustain food security goals in S. Asia.