More than one quadrillion gallons of the world’s freshwater is appropriated each year to support agriculture, industry, mining, and urbanization. These thirsty culprits, together with climate change, have stressed the global supply and quality of water, imperilling human health and the functioning of freshwater and coastal ecosystems alike. Mitigating water scarcity and pollution relies on management approaches and policy levers that reflect the most recent advances in scientific understanding and on skill in forecasting ecosystem responses and socio-economic consequences of potential management and policy actions.