In the past half-century, ready access to pumped wells has ushered in a worldwide “explosion” of groundwater development for municipal, industrial, and agricultural supplies. Globally, groundwater withdrawals total 750–800 km/year (Shah et al. 2000). Economic gains from groundwater use have been dramatic. However, in many places, groundwater reserves have been depleted to the extent that well yields have decreased, pumping costs have risen, water quality has deteriorated, aquatic ecosystems have been damaged, and land has irreversibly subsided. Groundwater depletion is the inevitable and natural consequence of withdrawing water from an aquifer. Theis (1940) showed that pumpage is initially derived from removal of water in storage, but over time is increasingly derived from decreased discharge and/or increased recharge. When a new equilibrium is reached, no additional water is removed from storage. In cases of fossil or compacting aquifers, where recharge is either unavailable or unable to refill drained pore spaces, depletion effectively constitutes permanent groundwater mining. In renewable aquifers, depletion is indicated by persistent and substantial head declines. Excessive groundwater depletion affects major regions of North Africa, the Middle East, South and Central Asia, North China, North America, and Australia, and localized areas throughout the world. Although the scope of the problem has not been quantified globally, on-going analysis by the senior author indicates that about 700–800 km of groundwater has been depleted from aquifers in the US during the 20th century. One of the best documented cases is the 450,000 km High Plains aquifer system in the central US, where the net amount of water removed from storage during the 20th century was more than 240 km—a reduction of about 6% of the predevelopment volume of water in storage (McGuire et al. 2003). In some of the most depleted areas, use of groundwater for irrigation has become impossible or cost prohibitive (Dennehy et al. 2002). In some cases, removing the most easily recoverable fresh groundwater leaves a residual with inferior water quality. This is due, in part, to induced leakage from the land surface, confining layers, or adjacent aquifers that contain saline or contaminated water. In coastal areas, where many of the world’s largest cities are located, the available volume of fresh groundwater is reduced by seawater intrusion and upconing, which in turn are caused by head declines in the aquifer. As depletion continues worldwide, its impacts worsen, portending the need for objective analysis of the problem and its possible solutions. This essay examines future options for evaluating and managing groundwater depletion in a changing physical and social landscape.