The petroleum industry now handles an estimated 15 million bbl/day (2.4 million m3/day) of wastewater coproduced from unconventional development in the Permian Basin region of west Texas and southeast New Mexico. Most of this wastewater is disposed by injection into subsurface reservoirs at multiple levels. In the areas impacted, this injection has caused reservoir pressurization, fault reactivation, high rates of problematic earthquakes, uplift of the ground surface, and threats to the surface environment and ongoing petroleum development. Understanding and mitigating injection-induced earthquakes is inherently technically demanding and requires deep integration across geoscience and reservoir engineering disciplines. Published in this special issue of the AAPG Bulletin titled “The Geology of Injection-Induced Earthquakes in the Midland Basin Region” are six technically interlinked papers that address geological, geomechanical, and reservoir engineering aspects of the production and injection of coproduced wastewater in the Permian Basin region and the resulting induced seismicity hazard.