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Over 350 vertebrate species rely on sagebrush ecosystems for their existence within all or portions of their lifespans. The sagebrush ecosystem faces two types of threats � persistent ecosystem threats, those that are difficult to regulate and are managed via ecological approaches, and threats due to land uses and development, those threats that can be regulated, but due to population growth and resource demands will likely continue. Persistent ecosystem threats include the spread of invasive species, conifer expansion, altered fire regimes, and climate change. Land use and development threats include cropland conversion, energy development, recreation, wild horse and burro use, and improper livestock grazing. The importance of these threats and their priority for management across the sagebrush biome changes depending the location. Therefore, a biome-wide management or mitigation plan for dealing with these threats will likely be unsuccessful unless it incorporates a multi-scale approach. Similarly, management scenarios developed in isolation for a single local area, without considerations of the surrounding landscape, may mitigate a local threat, but may not benefit habitat improvement for a species that requires larger scale considerations. Fragmentation of sagebrush habitats may leave sagebrush-dependent species without sufficient habitat or habitat connections for genetic exchanges among surrounding populations, thereby leaving populations vulnerable to inbreeding depression and further jeopardizing the isolated populations. Mitigation plans for reducing threats and improving habitats will likely benefit sagebrush-dependent landscape species when habitat connectivity is included. Strategic decisions that assess threat mitigation at multiple scales may reduce costs relative to benefits gained in habitat improvement for sagebrush-dependent species.