We are developing and applying an interdisciplinary system approach (involving analyses of GRACE gravity, remote sensing, and geochemical data, along with hydrologic modeling) to assess and calibrate GRACE data for monitoring groundwater recharge, discharge, and flow in large-scale aquifers. The Nubian Aquifer of North Africa was chosen as a test site, because its extensive areal distribution allows temporal gravity variations to be detected with accuracy; its hyperarid conditions facilitate calibration of GRACE gravity data; and its potential for demonstrating the utility of GRACE data to resolve issues pertaining to recharge and discharge rates, the magnitude and direction of groundwater flow, and the connectivity of subbasins. Results obtained from this research could provide straightforward techniques for monitoring storage variability in groundwater resources in arid and semi-arid countries worldwide. This work is being conducted jointly by scientists from Western Michigan University, Argonne National Laboratory, the University of Illinois at Chicago, the Macquarie University (Sydney, Australia), and Cairo University (Cairo, Egypt). The work will build on two decades of collaborative research efforts with our Egyptian colleagues.