To investigate the kinematics of the Adriatic region, we integrate continuous and episodic GPS measurements with Mw > 4.5 earthquake slip vectors selected from the Regional Centroid Moment Tensor catalogue. Coherent motion of GPS sites in the Po Valley, in Apulia, and in the Hyblean Plateau allows us to estimate geodetically constrained angular velocities for these regions. The predictions of the GPS-inferred angular velocities are compared with the earthquake slip vectors, showing that the seismically expressed deformation at the microplate boundaries is consistent with the observed geodetic motion. The remarkable consistency between geodetic, seismological, and geological evidence of active tectonics suggests that active deformation in the central Adriatic is controlled by the relative motion between the Adria and Apulia microplates. The microplates' angular rotation rates are then compared with the rotation rates calculated with a simple block model supporting the hypotheses (1) that Apulia forms a single microplate with the Ionian Sea and possibly with the Hyblean region and (2) that Adria and Apulia rotate in such a way as to accommodate the Eurasia-Nubia relative motion. We suggest that the present-day microplate configuration follows a recent fragmentation of the Adriatic promontory that during the Neogene rigidly transferred the Africa motion to the orogenic belts that now surround the Adriatic region.