The geological “source” of earthquakes in the Illinois basin, beyond the New Madrid seismic zone (NMSZ), has remained elusive despite the wealth of drill hole and surface mapping data. During the past several years, we have used deep, conventional, and shallow high-resolution seismic reflection methods in order to (1) reveal the detailed structure of folds and fault zones developed within the Paleozoic section as previously mapped from drill hole data, (2) detect major zones of faulting within the deep crust, and (3) delineate zones of Neogene-Quaternary-age deformation. In general, our studies of industry reflection data indicate that most of the major Paleozoic folds and monoclines are cored by high-angle reverse faults in a Laramide-style of deformation. Such faults have propagated up from the Precambrian basement and thus seem to provide “pre-existing zones of weakness” available for reactivation. However, the study of seismogenesis in the region has been hampered by the fact that earthquake epicenters frequently do not correlate with such Paleozoic structures and that the larger (mb > 3.0) earthquakes typically have focal depths well into the Precambrian crystalline crust. Reprocessing of selected industry reflection profiles, which extends the record lengths into seismogenic depths within the middle crust, reveals that the hypocenter of a thrust-fault mechanism event (1968.11.09) correlates spatially to an isolated dipping reflector sequence in the middle crust and that the focus of a strike-slip mechanism event (1987.06.10) closely matches a vertical reflector-defined fault zone in Precambrian crust. In these two cases, the epicenters do not obviously correlate with structures expressed in the Paleozoic section, suggesting “blind” reactivation of Precambrian structures. New seismic acquisition complemented by drilling, trenching, and outcrop mapping in southern Illinois, just north of the NMSZ, demonstrates Quaternary-age faulting in the northern Mississippi embayment. We have found narrow grabens localized over Paleozoic-age Fluorspar Area faults into which latest Cretaceous, Paleocene, and Eocene sediments were down-dropped. The bounding faults of the grabens have been active during Neogene through middle Pleistocene time and include displacements of up to 150 m.