The southern end of the Illinois Basin is one of the most structurally complex regions in the Midcontinent United States. Two major structural elements characterize this part of the basin: (1) A broad southwestward-plunging cratonic depression extends across central Illinois and southwestern Indiana. Investigations of historical and prehistorical earthquakes in this part of the basin indicate that moderate to high earthquake potential exists; the seismogenic sources, however, remain enigmatic. (2) The southernmost part of the basin is underlain by the Reelfoot Rift and Rough Creek Graben, a rift system that formed during late Precambrian to Middle Cambrian time. Geodynamic processes operating within the rift since the late Precambrian have had a major influence on the tectonic, diagenetic, and depositional history of the region. In addition, tectonic compressive stress appears to be reactivating ancient faults within the Reelfoot Rift, resulting in coherent linear segments of earthquake epicenters called the New Madrid Seismic Zone. Geological and geophysical information suggests that the cause of earthquakes in the New Madrid Seismic Zone is unrelated to that in the region north of the rift system.