A new seismotectonic model for the outer Central-Southern Apennines, including the epicentral area of the 2002 Molise seismic sequence, and adjacent foreland is proposed. The seismic sequence is related to foreland deformation affecting the Adriatic lithosphere. Such deformation is characterized by active NW–SE compression, resulting in the reactivation, mainly as dextral strike-slip faults, of pre-existing east–west oriented structures, both offshore and onshore. One of these structures is interpreted to extend westward and to reach the epicentral area of the recent earthquakes. NW–SE compression, ultimately related with Africa–Europe plate convergence, and uplift would essentially control the active tectonics of the analysed region.