In arid regions of rapid economic and population growth, adverse effects of droughts are likely to be increasingly serious. This article presents an introduction and overview of the papers collected in this special issue of the Water Resources Bulletin. The papers report on the second phase of a study of the impacts of and responses to a potential severe sustained drought in the Colorado River Basin in the southwestern U.S. The analyses were performed by a consortium of researchers from universities and the private sector located throughout the Basin.