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Convergence of the Africa, Arabia, and Eurasia plates and the westward escape of Anatolia have resulted in an evolving plate boundary zone in the Eastern Mediterranean. The current location and nature of the plate boundary between the Anatolian and the African plate is difficult to trace due to the scattered crustal earthquakes and the absence of deep ones. We examine various types and locations for the plate boundary as constrained by seismicity, seismic reflection studies, tomographic studies, and geodetic measurements and we use a spherical plane stress finite element model to test these possibilities. In our regional model, we impose the convergence of Africa, Arabia, and stable Eurasia by applying GPS-derived velocities in the far-field, as well as the roll-back of the Hellenic trench to solve for regional deformation. Model velocity and stress fields are compared with GPS-derived velocities and stress directions from focal mechanism solutions. We find that the plate boundary via the Pliny and Strabo trenches, the Anaximander Mountains, the Eratosthenes Seamount collisional segment, and the Latakia-Larnaka ridges gives the best fit to the data. The Anaximander Mountains plate boundary has both down-dip and strike-slip motions, and the Latakia segment is pure strike-slip. The Cyprus subduction contact is 42% locked. From a combined analysis of indicators for long-term deformation (predominantly slip-rates on major faults) and model results we infer that this southern plate boundary configuration may have existed since the Late Pliocene. [ABSTRACT FROM AUTHOR]