Water resources are subject to and an integral part of global change and globalization. Interdependencies of water resources with other ecological and social systems exist at all spatial scales. They can expose water resources to exogenous pressures originating in other regions and/or sectors (‘teleconnections’). Non-linear responses to these pressures can disturb the hydrology of ecosystems or whole regions and pose threats to water security and water-related goods and services. Water management and governance have not yet adapted to these cross-scale and cross-sectoral interdependencies and their dynamics and associated uncertainties. This paper highlights some key biophysical, socio-economic and institutional teleconnections in the global water system, such as those driven by atmospheric circulations and virtual water trade, and it outlines integrated and adaptive management and governance strategies. Water has to be recognized by a wide range of sectors and actors as a driver of change and, at the same time, impacted by these changes. Water needs have to be addressed consistently in climate, energy, trade, agricultural, development and other policies at all scales.