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Conservation of imperiled species often demands addressing a complex suite of threats that undermine species viability. Regulatory approaches, such as the US Endangered Species Act (1973), tend to focus on anthropogenic threats through adoption of policies and regulatory mechanisms. However, persistent ecosystem-based threats, such as invasive species and altered disturbance regimes, remain critical issues for most at-risk species considered to be conservation-reliant. We describe an approach for addressing persistent ecosystem threats to at-risk species based on ecological resilience and resistance concepts that is currently being used to conserve greater sage-grouse (Centrocercus urophasianus) and sagebrush ecosystems. The approach links biophysical indicators of ecosystem resilience and resistance with species-specific population and habitat requisites in a risk-based framework to identify priority areas for management and guide allocation of resources to manage persistent ecosystem-based threats. US federal land management and natural resource agencies have adopted this framework as a foundation for prioritizing sage-grouse conservation resources and determining effective restoration and management strategies. Because threats and strategies to address them cross-cut program areas, an integrated approach that includes wildland fire operations, postfire rehabilitation, fuels management, and habitat restoration is being used. We believe this approach is applicable to species conservation in other largely intact ecosystems with persistent, ecosystem-based threats. © Published by Elsevier Inc. on behalf of The Society for Range Management. The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact lbry-journals@email.arizona.edu for further information.