Grain production per unit of land will need to more than double over this century to address rising population and demand. This at a time when the procedures that have delivered increased yields over the past 50 years may have reached their ceiling for some of the world’s most important crops. Rising global temperature and more frequent droughts will act to drive down yields. The projected rise in atmospheric [CO2] by mid-century could in theory increase crop photosynthesis by over 30%, but this is not realized in grain yields in current C3 cultivars in the field. Emerging understanding of gene networks controlling responses to these environmental changes indicates biotechnological opportunities for adaptation. Considerably more basic research, particularly under realistic field conditions, is critical before these opportunities can be adequately understood and validated. Given the time needed between discovery in a model plant species and translation to traits or stacked changes in a commercial grain crop cultivar, there is an urgent need to vigorously pursue and develop these opportunities now.