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Sagebrush ecosystems and the flora and fauna they support are under threat. These threats are especially formidable for Wyoming big sagebrush, occupying the warmer-drier spectrum of these ecosystems. Loss of sagebrush has been the result of disturbance and weed encroachment; however, another underlying and increasingly important factor is climate change. Climate change information has to be an integral part of both research and management. For some areas of sagebrush, the notion of restoring to pre-disturbance conditions may be flawed. For example, the climatic niche of Wyoming big sagebrush is expected to decrease by about one-third by 2060 with much of the predicted loss occurring in the Great Basin. Moreover, niche modeling of ecoregions suggest southern and lower elevations of the sagebrush ecosystem will become ecotonal or transition to Mojave Desert. To mitigate the effects of climate change, disturbance and weeds, research should consider: 1) what native species will be suitable for future climates, 2) whether these species bear life-history characters and traits that would make them competitive against weeds, and 3) which populations within these species would be best adapted for assisted migration. I will discuss potential candidate species for assisted migration to fill the void left by sagebrush, populations that could provide higher fitness, and finally, the context and the potential role of breeding.