Changes in “blue water”, which is the total supply of fresh water available for human extraction over land, are quite closely related to changes in runoff or equivalently precipitation minus evaporation, P − E. This article examines how climate change-driven re-cent past and future changes in the regional water cycle relate to blue water availability and changes in human blue water demand. Although at the largest scales theoretical and numerical model predictions are in broad agreement with observations, at continental scales and below models predict large ranges of possible future P − E and runoff especially at the scale of individual river catchments and for shorter timescale subseasonal floods and droughts. Nevertheless, it is expected that the occurrence and severity of floods will increase and that of droughts may increase, possibly compounded by human-driven non-climatic changes such as changes in land use, dam water impoundment, irrigation and extraction of groundwater. Contemporary assessments predict that increases in 21stcentury human water extraction in many highly-populated regions are unlikely to be sustainable given projections of future P − E. To reduce uncertainty in future predictions, there is an urgent need to improve modeling of atmospheric, land surface and human processes and how these components are coupled. This should be supported by maintaining the observing network and expanding it to improve measurements of land surface, oceanic and atmospheric variables. This includes the development of satellite observations stable over multiple decades and suitable for building reanalysis datasets appropriate for model evaluation.