This article, published in *Nature* in 2010, presents a comprehensive global synthesis of the threats to human water security and biodiversity. The authors, led by C. J. Vörösmarty, use a spatial framework to quantify multiple stressors and their downstream impacts, finding that nearly 80% of the world's population is exposed to high threats. They highlight that while technological investments have improved water security in wealthy nations, they have not addressed underlying causes and left the poor vulnerable. The study also reveals that 65% of continental discharge habitats are moderately to highly threatened, emphasizing the need for precautionary investments. The cumulative threat framework offers a tool for prioritizing policy and management responses, suggesting that limiting threats at their source is more effective than costly remediation. The authors conclude that without major policy and financial commitments, the challenges to freshwater systems will persist, leading to social instability and environmental degradation.This article, published in *Nature* in 2010, presents a comprehensive global synthesis of the threats to human water security and biodiversity. The authors, led by C. J. Vörösmarty, use a spatial framework to quantify multiple stressors and their downstream impacts, finding that nearly 80% of the world's population is exposed to high threats. They highlight that while technological investments have improved water security in wealthy nations, they have not addressed underlying causes and left the poor vulnerable. The study also reveals that 65% of continental discharge habitats are moderately to highly threatened, emphasizing the need for precautionary investments. The cumulative threat framework offers a tool for prioritizing policy and management responses, suggesting that limiting threats at their source is more effective than costly remediation. The authors conclude that without major policy and financial commitments, the challenges to freshwater systems will persist, leading to social instability and environmental degradation.