Groundwater is the Earth's most extracted raw material, with almost 1,000 cubic kilometers per year (800 million acre-feet per year) of groundwater pumped from aquifers around the world. Approximately 70% of groundwater withdrawals worldwide are used to support agricultural production systems. This percentage is even higher in arid and semi-arid areas, where the only consistent source of irrigation water is groundwater. In these regions, however, the use of groundwater typically far exceeds the rate at which it is naturally replenished, indicating that these critical groundwater resources are being slowly depleted. Within the United States, groundwater depletion has occurred in many important agricultural production regions, including the Great Plains Region, the Central Valley of California, the Mississippi Embayment Aquifer, aquifers in southern Arizona, and smaller aquifers in many western states. This issue paper reviews the causes and consequences of groundwater depletion, with a focus on impacts to agriculture as the largest sector of groundwater use. This understanding can aid in developing effective policies and practices for groundwater development, use, and management.