The two-part Science Framework for Conservation and Restoration of the Sagebrush Biome published by the U.S. Forest Service Rocky Mountain Research Station is a new, multi-scale approach to management of sagebrush ecosystems. The product of an extensive collaboration between State and Federal agencies and universities, it employs science on ecological resilience to disturbance and resistance to invasive species (like cheatgrass), along with Greater sage-grouse habitat requirements, to improve conservation planning and help prioritize management actions. Prioritized areas and management strategies can be refined by managers and stakeholders at the local scale based on higher resolution data and local knowledge. Part 1 of the Framework describes a geospatial approach for overlaying information on ecosystem resilience and resistance, species habitats, and predominant threats. A resilience and resistance matrix is provided to help managers evaluate risks and determine appropriate management strategies. Part 2 focuses on specific management concerns, including: adaptive management and monitoring, climate adaptation, wildland fire and vegetation management, invasive plant management, National Seed Strategy concepts, livestock grazing management, wild horse and burro considerations, and integration and tradeoffs. The Science Framework (and this article) include links to data, maps, and models that are useful in sagebrush ecosystem and Greater sage-grouse management. The Science Framework is intended to be adaptive and will be updated as additional data become available on other values and species at risk.