With rivers in critical regions already exploited to capacity throughout the world and groundwater overdraft as well as large-scale contamination occurring in many areas, we have entered an era in which multiple simultaneous stresses will drive water management. Increasingly, groundwater resources are taking a more prominent role in providing freshwater supplies. We discuss the competing fresh groundwater needs for human consumption, food production, energy, and the environment, as well as physical hazards, and conflicts due to transboundary overexploitation. During the past 50 years, groundwater management modeling has focused on combining simulation with optimization methods to inspect important problems ranging from contaminant remediation to agricultural irrigation management. The compound challenges now faced by water planners require a new generation of aquifer management models that address the broad impacts of global change on aquifer storage and depletion trajectory management, land subsidence, groundwater-dependent ecosystems, seawater intrusion, anthropogenic and geogenic contamination, supply vulnerability, and long-term sustainability. The scope of research efforts is only beginning to address complex interactions using multiagent system models that are not readily formulated as optimization problems and that consider a suite of human behavioral responses.