A global village, an inter-connected world, a harmonious scientific community: these are some of the well-quoted end points of science diplomacy. As we strive to understand and mitigate challenges in climate change, energy and resource efficiency, health and demographic change, food security, and the digital divide, global partnerships must be built and sustained. It is not easy. Neither is a one-size-fits-all approach always the best option. Protecting difference and promoting winner-takes-all scientific competition is equally important. This high-profile session spotlights decision-makers from Brussels, Cape Town, and Washington responsible for striking this balance and influencing the largest budgets in global science. Their mandate is to place discovery and innovation at the core of international politics. Their success is measured against creating the necessary knowledge, jobs, and growth to see the developed and developing world through the economic downturn. Their goal of achieving sustainable development and alleviating poverty is shared. An important focus will be Africa’s determination to not only harness science and technology for the continent’s development, but to become a full and active partner in global knowledge partnerships. Progress toward a European Innovation Union with dynamic international cooperation links will be assessed, and U.S. insights into concrete actions and the strong international dimension required will be examined. Best practices and pitfalls will be identified.