The management of water resources in arid and semiarid areas has long been a challenge, from ancient Mesopotamia to the modern southwestern United States. As our understanding of the hydrological and climatological cycles has improved, and our ability to manipulate the hydrologic cycle has increased, so too have the challenges associated with managing a limited natural resource for a growing population. Modern civilization has made remarkable progress in water management in the past few centuries. Burgeoning cities now survive in desert regions, relying on a mix of simple and complex technologies and management systems to bring adequate water and remove wastewater. These systems have permitted agricultural production and urban concentrations to expand in regions previously thought to have inadequate moisture. However, evidence is also mounting that our current management and use of water is unsustainable. Physical, economic, and ecological limits constrain the development of new supplies and additional water withdrawals, even in regions not previously thought vulnerable to water constraints. New kinds of limits are forcing water managers and policy makers to rethink previous assumptions about population, technology, regional planning, and forms of development. In addition, new threats, especially the challenges posed by climatic changes, are now apparent. Sustainably managing and using water in arid and semiarid regions such as the southwestern United States will require new thinking about water in an interdisciplinary and integrated way. The good news is that a wide range of options suggest a roadmap for sustainable water management and use in the coming decades.