A large body of evidence collected over local domains shows that human interactions with the hydrologic cycle are characterized by mismanagement and ecosystem impairment. The countless human decisions and resulting actions that seek to optimize water security for humans at the local scale today accumulate as global syndromes of increasing environmental stress. A common feature of this globalization of water problems is the legacy of poor governance, which is deeply embedded into the fabric of contemporary hydrologic and biogeochemical cycles. This paper briefly explores the evolution of global-scale studies of the hydrologic cycle and the pivotal role that humans play in shaping modern water systems. We review key concepts that emerged over the last one-to-two decades that have motivated acceptance of the legitimacy of a fully global-scale perspective. Advances in diagnosing the broad-scale syndromes today set the stage for a next phase of study, crafting science-based solutions for sustainable water development as part of the broader global Rio+20 agenda.