Groundwater 18O/16O, 2H/1H, 13C/12C, 3H, and 14C data can help quantify molecular movements and chemical reactions governing groundwater recharge, quality, storage, flow, and discharge. Here, commonly applied approaches to isotopic data analysis are reviewed, involving groundwater recharge seasonality, recharge elevations, groundwater ages, paleoclimate conditions, and groundwater discharge. Reviewed works confirm and quantify long held tenets: (i) that recharge derives disproportionately from wet season and winter precipitation; (ii) that modern groundwaters comprise little global groundwater; (iii) that “fossil” (>12,000‐year‐old) groundwaters dominate global aquifer storage; (iv) that fossil groundwaters capture late‐Pleistocene climate conditions; (v) that surface‐borne contaminants are more common in younger groundwaters; and (vi) that groundwater discharges generate substantial streamflow. Groundwater isotope data are disproportionately common to midlatitudes and sedimentary basins equipped for irrigated agriculture, but less plentiful across high latitudes, hyperarid deserts, and equatorial rainforests. Some of these underexplored aquifer systems may be suitable targets for future field testing.