An integrated approach for assessing the availability of groundwater under conditions of 'global-change' is presented. The approach is embedded in the DANUBIA system developed by the interdisciplinary GLOWA-Danube Project to simulate the interaction of natural and socio-economic processes within the Upper Danube Catchment (UDC, 77,000 km(2) and located in parts of Germany, Austria, Switzerland and Italy). The approach enables the quantitative assessment of groundwater bodies (zones), which are delineated by intersecting surface watersheds, regional aquifers, and geomorphologic regions. The individual hydrogeological and geometrical characteristics of these zones are accounted for by defining characteristic response times and weights to describe the relative significance of changes in variables (recharge, groundwater level, groundwater discharge, river discharge) associated with different states. These changes, in each zone, are converted into indices (GroundwaterQuantityFlags). The motivation and particularities of regional-scale groundwater assessment and the background of GLOWA-Danube are described, along with a description of the developed methodology. The approach was applied to the UDC, where several different climate scenarios (2011-2060) were evaluated. A selection of results is presented to demonstrate the potential of the methodology. The approach was inspired by the European Water Framework Directive, yet it has a stronger focus on the evaluation of global-change impacts.