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Sagebrush ecosystems and the species that depend upon them are at risk due to a suite of persistent ecosystem and anthropogenic threats, and managers and policy makers are seeking strategic, multiscale approaches for species conservation and ecosystem restoration. Recently, a Science Framework for Conservation and Restoration of the Sagebrush Biome has been developed that provides a science-based approach for prioritizing areas for management at large landscape scales and determining effective management strategies at project and site scales. An understanding of ecosystem resilience to disturbance, i.e., recovery potential, and resistance to invasive annual grasses underpins the approach. First, areas are prioritized for management using a geospatial process that overlays information on ecosystem resilience and resistance, species habitats, and predominant threats at the ecoregional/Greater sage-grouse management zone scale. A resilience and resistance habitat matrix helps decision makers evaluate risks and determine appropriate management strategies at these larger scales. Then, prioritized areas and management strategies are refined by managers and stakeholders based on higher resolution data and local knowledge at project to site scales. Ecological type descriptions and state-and-transition models characterized according to relative resilience and resistance are key tools in the step-down process. Factsheets, field guides, and field workshops have been developed through the Great Basin Fire Science Exchange and its partners to facilitate application of the approach. The geospatial data, maps, and models are provided through the U.S. Geological Survey (USGS) ScienceBase and Bureau of Land Management (BLM) Landscape Approach Data Portal, and a visualization tool for the different geospatial data layers and maps is under development. This approach was incorporated into the Subregional Greater Sage-grouse EISs and a BLM Fire and Invasives Assessment Tool used to prioritize sage-grouse habitat for targeted management activities. US Forest Service has used a similar, threat-based process.