Food and agriculture systems have to undergo a profound transformation to become both more sustainable and more productive. This achievement requires the generation of new knowledge and enhanced translation of knowledge into use, entailing considerable efforts in terms of research and innovation. Research will need to integrate diverse disciplines and perspectives in order to address multiple objectives at the field, landscape, and value-chain levels. A systemic approach oriented toward user needs must be a part of agricultural innovation systems and include farmers, enterprises, and bridging institutions. It will require sustained and predictable public funding as well as higher private investment for generation and transfer of technologies, building upon successful experiences.