Dealing with the challenges of global change requires a transition not only in society but also in the scientific community. Despite continued claims for more inter-disciplinary approaches, progress to date has been slow. This paper elaborates on the need for innova- tion in methodologies and knowledge, on the one hand, and methods and data, on the other, to build the foundations for dealing with the challenges from global change. Three questions related to the nature of global change, the dynamics of sustainability transitions and the role of human agency guide analyses on the state of the art, barriers for innovation and need for action. The analyses build on literature reviews, expert workshops and surveys which were conducted under the umbrella of RESCUE, a foresight activity funded by the European Science Foundation. The major recommendations focus on integrating environmental and human dimensions, bridging scales, data and knowledge for global change research and overcoming structural constraints to make global change research more policy relevant.