The sagebrush (Artemisia spp.) biome has changed since settlement by Europeans. The current distribution, composition and dynamics, and disturbance regimes of sagebrush ecosystems have been altered by interactions among disturbance, land use, and invasion of exotic plants. In this chapter, we present the dominant factors that have influenced habitats across the sagebrush biome. Using a large-scale analysis, we identified regional changes and patterns in “natural disturbance”, invasive exotic species, and influences of land use in sagebrush systems. Number of fires and total area burned has increased since 1980 across much of the sagebrush biome. Juniper (Juniperus spp.) and pinyon (Pinus spp.) woodlands have expanded into sagebrush habitats at higher elevations. Cheatgrass (Bromus tectorum), an exotic annual grass, has invaded much of lower elevation, more xeric sagebrush landscapes across the western portion of the biome. Consequently, synergistic feedbacks between habitats and disturbance (natural and human-caused) have altered disturbance regimes, plant community dynamics and contributed to loss of sagebrush habitats and change in plant communities. Habitat conversion to agriculture has occurred in the highly productive regions of the sagebrush biome and influenced up to 56% of the Conservation Assessment area. Similarly, urban areas, and road, railroad, and powerline networks fragment habitats, facilitate predator movements, and provide corridors for spread of exotic species across the entire sagebrush biome. Livestock grazing has altered sagebrush habitats; the effects of overgrazing combined with drought on plant communities in the late 1880s and early 1900s still influences current habitats. Management of livestock grazing has influenced sagebrush ecosystems by habitat treatments to increase forage and reduce sagebrush and other plant species unpalatable to livestock. Fences, roads, and water developments to manage livestock movements have further influenced the landscape and increased access into sagebrush habitats. Energy development also influenced sagebrush landscapes by construction of wells, access roads, and pipelines. Treatments to restore sagebrush are becoming a major emphasis of land management agencies. However, revegetation and rehabilitation treatments are limited by the financial, biological, and technological resources needed to restore sagebrush landscapes that function at the spatial and temporal scales used by sage-grouse (Centrocercus urophasianus)