Regional aquifer-system compaction and land subsidence accompanying groundwater abstraction in susceptible aquifer systems in the USA is a challenge for managing groundwater resources and mitigating associated hazards. Developments in the assessment of regional subsidence provide more information to constrain analyses and simulation of aquifer-system compaction. Current popular approaches to simulating vertical aquifer-system deformation (compaction), such as those embodied in the aquitard drainage model and the MODFLOW subsidence packages, have proven useful from the perspective of regional groundwater resources assessment. However, these approaches inadequately address related local-scale hazards—ground ruptures and damages to engineered structures on the land surface arising from tensional stresses and strains accompanying groundwater abstraction. This paper presents a brief overview of the general approaches taken by the U.S. Geological Survey toward understanding aquifer-system compaction and subsidence with regard to a) identifying the affected aquifer systems; b) making regional assessments; c) analyzing the governing processes; and d) simulating historical and future groundwater flow and subsidence conditions. Limitations and shortcomings of these approaches, as well as future challenges also are discussed