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Meeting sustainable development goals will require action on a number of fronts, including harnessing and maximizing the potential of technological innovation. Examples of such technologies include carbon capture and storage systems, more efficient irrigation methods, essential medicines, household water purification devices, and manufacturing processes that minimize waste and pollution. While some needed innovations can be fostered through existing public and private mechanisms at the national level, such efforts have proven inadequate to meet global sustainability goals, particularly with regard to meeting the needs of the world’s poorest, most vulnerable or marginalized in current and future generations. Too often, technologies are either not developed at all for lack of a sufficiently profitable market, or if developed, are not accessible or well-adapted to end-user needs. This Program initiative seeks to advance knowledge and understanding of how to equitably improve the functioning of the “global innovation system” for sustainable development technologies. We are conducting a comparative study of how well the system functions to meet five sustainable development needs (food, energy, health, manufactured goods, and water), with a special focus on equity. The initiative is examining specific cases of “system interventions” (e.g., policy interventions, institutional innovations, new approaches to shaping the innovation process) intended to strengthen the global innovation system, with the broader aim of developing policy recommendations that draw from, and are generalizable across, multiple sectors. The findings will contribute to realizing the potential of science and technology to meet the most pressing sustainable development challenges.