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Climate change and population growth are contributing to a growing global freshwater crisis that is exacerbating agricultural water scarcity and compromising food security and public health. In light of these challenges, the increased reliance on nontraditional irrigation water sources, such as reclaimed or recycled water, is emerging as a potentially viable strategy to address water and food insecurity worldwide. This editorial provides an overview of the global need for agricultural water reuse and outlines the environmental and public health impacts associated with this practice. Policy implications, including an emphasis on "One Water" approaches, are discussed. Finally, the editorial leads off a Special Issue that includes a collection of articles reporting on the initial research and extension/outreach findings of CONSERVE: A Center of Excellence at the Nexus of Sustainable Water Reuse, Food and Health, funded by the U.S. Department of Agriculture, National Institute of Food and Agriculture. Taken together, this compilation of articles addresses the overarching theme that transdisciplinary teams are key with regard to moving the science of agricultural water reuse forward to achieve water and food security and advance public health in a changing climate.