In the winter of 1811-12, three of the largest historic earthquakes in the United States occurred near New Madrid, Missouri. Seismicity continues to the present day throughout a tightly clustered pattern of epicenters centered on the bootheel of Missouri, including parts of northeastern Arkansas, northwestern Tennessee, western Kentucky, and southern Illinois. In 1990, the New Madrid seismic zone/central United States became the first seismically active region east of the Rocky Mountains to be designated a priority research area within the National Earthquake Hazards Reduction Program (NEHRP). This professional paper is a collection of papers, some published separately, presenting results of the newly intensified research program in this area. Major components of this research program include tectonic framework studies, seismicity and deformation monitoring and modeling, improved seismic hazard and risk assessments, and cooperative hazard mitigation studies.