It is becoming increasingly recognized that our collective ability to tackle complex problems will require the development of new, adaptive, and innovative institutional arrangements that can deal with rapidly changing knowledge and have effective learning capabilities. In this paper, we applied a knowledge-systems perspective to examine how institutional innovations can affect the generation, sharing, and application of scientific and technical knowledge. We report on a case study that examined the effects that one large innovative organization, The Global Fund to Fight AIDS, Tuberculosis, and Malaria, is having on the knowledge dimensions of decision-making in global health. The case study shows that the organization created demand for new knowledge from a range of actors, but it did not incorporate strategies for meeting this demand into their own rules, incentives, or procedures. This made it difficult for some applicants to meet the organization's dual aims of scientific soundness and national ownership of projects. It also highlighted that scientific knowledge needed to be integrated with managerial and situational knowledge for success. More generally, the study illustrates that institutional change targeting implementation can also significantly affect the dynamics of knowledge creation (learning), access, distribution, and use. Recognizing how action-oriented institutions can affect these dynamics across their knowledge system can help institutional designers build more efficient and effective institutions for sustainable development.aid financing | governance | HIV/AIDS | knowledge transfer | science-policy interface T he importance of flexible, adaptive institutions in tackling complex problems is becoming increasingly recognized, and there is a call for institutional change that highlights the key role of knowledge and learning in the context of action and implementation (1, 2). As a result, institutions for sustainable development are undergoing rapid change. Existing centralized international and state-based systems are increasingly being complemented and challenged by new forms of collaboration, including public-private partnerships, multisector collaborations, and demand-led funding mechanisms (3). These changes are largely driven by dissatisfaction with the perceived inability of traditional institutions to move toward more sustainable development trajectories (4, 5) and pose new opportunities to link knowledge with action.In this study, we examined how one innovative, action-focused organization has affected the dynamics of knowledge sharing, generation, and application across their network of stakeholders using a theoretical framing based on the concept of knowledge systems. Building on work by Cash et al. (6) and van Kerkhoff and Lebel (7) for this project, we defined a knowledge system as a network of actors connected by social relationships, formal or informal, that dynamically combined knowing, doing, and learning to bring about specific actions for sustainable development (8). We were in...