At least 8 regional flow systems are inferred to exist in Trans-Pecos Texas. The best documented are those that discharge or discharged at major springs in Hudspeth, Jeff Davis, Pecos, and Reeves Counties. Some of these springs have ceased to flow or now flow at diminished rates. Data indicate that spring discharges have been gradually declining, and groundwater extraction threatens continued spring flows. Regional fracture trends in fractured, karstic Cretaceous and Permian carbonate rocks that adjoin thick basin fills in the Toyah Basin, the Salt Basin, and other bolsons connect the major recharge and discharge areas and localize discharge from carbonate aquifers. Analysis of fracture systems allows interpretation of regional flow systems and regional-scale permeability. Recharge is from fractures in the highlands, losing streams on proximal portions of alluvial fans, irrigation return flow, and interbasin flow. Discharge is to the springs, by wells, to salt flats, to the Rio Grande, and in the past to the Pecos River. Chemical and isotopic data confirm the inferred flow systems and that some of the spring flow recharged during the Pleistocene. Groundwater systems are evolving because of both climatic trends and anthropogenic effects. The springs at Balmorhea are partially recharged by regional flow that originates in the Salt Basin and flows through the Apache Mountains into the Toyah Basin. Both this system and the one discharging at Dell City are strongly influenced by fractures that follow regional structural trends. This is supported by: 1) fracture trace analyses; 2) groundwater geochemical data that identify hydrochemical facies and rock-water interactions; and 3) isotopic data that distinguish local from regional recharge and the strontium data trace a “plume” that corresponds to groundwater flow paths. Other regional flow systems are inferred because of the presence of high permeability carbonate rocks at depths; the semi-arid climate, discharge of thermal waters, and interpretation of potentiometric data.