Southwest Wyoming land managers face the challenge of ensuring the persistence of the region’s abundant wildlife and important habitats while providing for development of Nationally important energy and mineral resources. Driven by local and regional leaders, the Wyoming Landscape Conservation Initiative (WLCI) was officially launched in 2007 with support from the U.S. Department of the Interior. The WLCI mission is to implement a long-term, science-based program of assessing, conserving, and enhancing fish and wildlife habitats while facilitating responsible energy and other development through local collaboration and partnerships. As the principal agency charged with conducting WLCI science, the U.S. Geological Survey (USGS) provides multidisciplinary scientific- and technical-assistance support to WLCI partners and works to advance the overall scientific understanding of ecosystems in Southwest Wyoming. Fulfilling these roles entails evaluating the effectiveness of habitat treatments implemented by WLCI partners and collaborators, assessing the cumulative effects of energy development and other land-use changes on wildlife and habitat in the WLCI area, coordinating work activities with the WLCI community, and demonstrating how to integrate research findings into on-the-ground management actions. Work is guided by a Science Strategy based on management needs and by intensive coordination with WLCI partners. The framework for conducting WLCI research and technical assistance work includes Baseline Studies, Targeted Monitoring and Research, Data and Information Management, Integration and Coordination, and Decision-making and Evaluation.