Like many arid and semiarid regions, the Great Basin of the western United States is undergoing major ecological, social, and economic changes that are having widespread detrimental effects on the structure, composition, and function of native ecosystems. The causes of change are highly interactive and include urban, suburban, and exurban growth, past and present land uses, climate change, altered fire regimes, and rapid expansion of invasive species. Cumulative effects include vegetation type conversions, loss of watershed functioning, loss of native species, and diminished economic potential. The diversity and magnitude of issues require consensus on priority issues, and new and innovative research and management approaches that address larger spatial scales and longer time scales than in the past. Primary research coupled with large-scale assessments and effective monitoring strategies is needed to understand and track the ongoing changes. Prediction and modeling of alternative futures are needed for incorporation into the planning process and use as a basis for adaptive management, and management tools are needed to aid decision-making and implementation. Historically, research and management in arid and semiarid regions such as the Great Basin have been severely under-funded and altering current trajectories will require financial resources, political support, and effective policies and institutional mechanisms. Sustaining the ecosystems, resources, and human populations of these regions will require strong collaborative partnerships among research and management organizations to reduce overlap, leverage funds, and increase efficiency. Close involvement of all stakeholders is needed to obtain the needed support for making necessary changes in policies and management activities.