Large-scale relational databases and geographic information system tools are used to integrate temperature, pressure, and water geochemistry data from numerous wells to better understand regional-scale geothermal and hydrogeological regimes of the lower Paleozoic aquifer systems in the mid-continent and to evaluate their potential for geologic CO2 sequestration. The lower Paleozoic (Cambrian to Mississippian) aquifer systems in Kansas, Missouri, and Oklahoma comprise one of the largest regional-scale saline aquifer systems in North America. Understanding hydrologic conditions and processes of these regional-scale aquifer systems provides insight to the evolution of the various sedimentary basins, migration of hydrocarbons out of the Anadarko and Arkoma basins, and the distribution of Arbuckle petroleum reservoirs across Kansas and provides a basis to evaluate CO2 sequestration potential. The Cambrian and Ordovician stratigraphic units form a saline aquifer that is in hydrologic continuity with the freshwater recharge from the Ozark plateau and along the Nemaha anticline. The hydrologic continuity with areas of freshwater recharge provides an explanation for the apparent underpressure in the Arbuckle Group.