We tie together geological data, paleotectonic reconstruction, plate motion, and tomographic analysis to unravel the history of subduction and back arc extension of the eastern and central Mediterranean. In these two regions, extensional processes started contemporaneously, around 30 Myr ago, but with marked differences. In the eastern region, the Aegean basin opened slowly (∼1 cm/yr) behind a shallow dipping slab (40–45°). The corresponding high-velocity anomaly extends inside the upper mantle and can be also followed in the midmantle down to a depth of at least 1500 km. Its descent into the midmantle initiated most probably during the Late Cretaceous, and the trench moved northeastward, following the path of the Eurasian plate and under the persistent push of the African plate. Conversely, in the central Mediterranean region, subduction initiated later, and the motion of the subducting slab is confined to the upper mantle, causing punctuated and rapid episodes of back arc extension (Provençal and Tyrrhenian basins) behind a slab that dips steeply (75°). We explore the causes that control how the slab subducted and interacted with the lower, more viscous part of the mantle.