Groundwater is the Earth's most extracted raw material, with roughly 70% of global withdrawals used for agriculture—a share even higher in arid regions where use far exceeds natural replenishment. Significant aquifer depletion has occurred in key U.S. agricultural areas, including the Great Plains, California's Central Valley, the Mississippi Embayment, and aquifers in southern Arizona. This Issue Paper reviews causes and consequences of groundwater depletion with a focus on agricultural impacts, and discusses effective policies and practices for sustainable groundwater development and management.