Strait uplift due to isostasy played a pivotal role in the development and maintenance of a desiccated Mediterranean basin during the Late Miocene Messinian salinity crisis. New three-dimensional flexure models for the western Mediterranean suggest that most of the giant evaporite body was deposited before sea-level lowering. Any mechanism that subsequently caused a Mediterranean sea-level lowering by a few hundred meters during several thousand years sufficed to cause isostatic uplift and closure of the gateways, thus choking the Mediterranean to desiccation. Due to this isostatic feedback, multiple desiccation and reflooding phases driven by Milankovitch cycles are unlikely. When the Atlantic connection had been lost and sea level had dropped, a sizeable regional uplift of the Strait of Gibraltar developed that presented a formidable obstacle to reflooding. Rollback and steepening of the Gibraltar slab may have played a key role at the end of the Miocene by dynamically lowering the sill region, thus reinstating the oceanic connection.