For nearly half a century, the international wheat breeding system has delivered improved high yielding varieties of wheat that created (along with rice) the Green Revolution and underpinned strong growth in wheat productivity in irrigated and rainfed, developed and underdeveloped, regions. Future priorities for breeding and complementary sciences will still include yield but will also diversify in response to changing market demands and growing environments, particulary in developing countries. It is argued that in the coming decades research on wheat quality characteristics will become increasingly important to plant breeders, whose work will be supported by the development of markers and advanced tools from molecular biology. Breeders will have to contend with increased heat stress and variability stemming from climate change, which is expected to create regional winners, as the northern high latitudes grow warmer and moister, and losers, as the sub-tropics and tropics increasingly suffer from heat stress and drought. Yield response of improved varieties in farmers’ fields depends to a very great degree on sustainable systems management, which also is essential to reverse the ongoing degradation of agricultural resources. Finally, the importance of expanding the systems lens from farmers to policy makers, and of linking farmers, commerce, science, and policy is illustrated for the rice-wheat farming systems of South Asia.