Adaptive management is a powerful approach to management of social-ecological systems in circumstances with high uncertainty and high controllability. Cross-scale interactions increase uncertainty while managing. When undertaking adaptive management, although largely overlooked, it is important to account for spatial and temporal scales to mediate within- and cross-scale effects of management actions. This is particularly true when managing for multiple social and ecological goals. The iterative nature of an adaptive approach has the capacity to accommodate tradeoffs among different stakeholder priorities and multiple ecosystem attributes within and across scales. In this paper, we introduce multi-scale adaptive management of social-ecological systems and demonstrate the importance of this approach with case studies of the Great Plains of North America and the Platte River Basin in the United States. Adaptive management combined with a focus on scale and cross-scale interactions using the panarchy model of social-ecological systems can help to improve management outcomes.