Abstract The seismicity rate in the central United States is, for the most part, low compared to that in more active regions such as California. Occasionally, however, severe earthquakes do occur, and certain regions, such as the New Madrid seismic zone, are characterized by a seismicity level well above that in surrounding areas. Earthquakes in midplate regions have been considered to be enigmatic since they cannot easily be associated with major deformation as can earthquakes near plate margins. The past decade has, however, seen a large increase in our understanding of midplate earthquakes, particularly those in concentrated zones where seismic activity has been well monitored. For purposes of the present chapter we define the central United States as that region between the Appalachian and Rocky Mountains shown in Figure 1. The eastern boundary is taken to coincide with the eastern border of Ohio, to continue southward into West Virginia and to pass in a southwestward direction through a sliver of West Virginia, through eastern Kentucky and central Tennessee just west of the Appalachian Mountains. It continues in a southwestward direction through a corner of Alabama, intersects the state line of Mississippi at about 35.5° latitude, and coincides with the Alabama-Mississippi boundary southward to the Gulf Coast. The western boundary coincides with the western state lines of North Dakota, South Dakota, Nebraska, Kansas, Oklahoma, and the western boundary of the panhandle of Texas. It continues southward through west Texas to Mexico. The northern boundary is the international boundary between the United States