Although large and damaging earthquakes occur in the central and eastern United States (CEUS), no comprehensive and scientifically sound physical models have proven to be reliable indicators of where future large earthquakes are likely to occur in this region. This situation forces seismologists who are attempting to estimate the seismic hazard in CEUS to rely heavily on the observed record of seismicity as an indicator of where future large earthquakes are likely to occur. In this study, the hypothesis that seismicity delineates areas where large earthquakes are likely to occur in CEUS (as well as in other regions) is tested and statistically analyzed. These analyses are then used as a basis for quantifying and giving statistical bounds for the percentage of large earthquakes in CEUS that can be expected to occur in areas where previous earthquakes have occurred. Based on the data analyzed in this study, I estimate that at least two thirds to three fourths of the future large earthquakes in CEUS will occur in zones delineated by historical seismicity.