The reactivation of discontinuities in response to stress field variations was a common feature in the structural evolution of the Adriatic Block in the central Mediterranean. This elongate crustal element of African origin, which is characterized by a thick Mesozoic carbonate section, constitutes the foreland to the orogenic belts of the Apennines as well as the Dinarides. Between the Southern Apennines and the Dinarides, its northwest-southeast trending longitudinal fault trends are dissected by oblique discontinuities corresponding to prominent wrench zones, such as the east-west trending Mattinata Fault System. Field data from the Gargano Promontory in southeastern Italy, integrated with subsurface data from the adjacent Bradanic Trough, have revealed that the Mattinata Fault System during the Cretaceous acted as a transfer zone linking synsedimentary normal fault trends. In consequence of the Late Miocene through Early Pliocene paroxysm of Apenninic tangential shortening, it was reactivated in a sinistral sense with local convergent and divergent shearing according to the orientation of fault segments. The stress regime from the Late Pliocene on, instead, favored dextral strike slip. Some fault segments were unaffected by this complete reversal of relative motion as pre-existing longitudinal discontinuities accommodated a diffuse northward slip transfer, thereby allowing the partial preservation of earlier features.