||The Tethys Ocean existed between the continents of Gondwana and Laurasia from the Triassic to the Pliocene. Analyses of multiple biogeographic and phylogenetic histories reveal that the subsequent breakup of the Tethys greatly influenced the distributions of many species. The ancestral Tethyan realm broke into five biogeographic provinces, including the present-day East Pacific, West Atlantic, East Atlantic, Mediterranean Sea, and Indo-West Pacific. Palaeogeographic maps illustrate the Mesozoic Atlantic opening, the Cenozoic closure of the Tethys, the Messinian Salinity Crisis, the mid-Miocene closure of the Central American Seaway, and Quaternary geological changes. Further, we consider Cenozoic sea-level changes and the formation of freshwater habitats. These reconstructions allow assessment of patterns of aquatic diversification for marine and freshwater animals, and comparison of vicariance and dispersal processes. Estimated divergence times indicate that fragmentation of the Tethys was responsible for the vicariant speciation of aquatic animals because these dates are consistent with associated tectonic events. The opening of the Atlantic Ocean during the Cretaceous is responsible for the earliest isolation between the West and East Atlantic. The mid-Miocene closure of the Tethys, which blocked global equatorial currents, appears to have isolated the Atlantic/Mediterranean Sea and Indo-West Pacific. Finally, formation of the Isthmus of Panama isolated East Pacific and West Atlantic marine organisms. Dispersals related to the Messinian Salinity Crisis and Quaternary sea-level changes influenced population structuring. Tethyan changes affected marine habitats, created new freshwater habitats, inland caves and ancient lakes along the Alps and Himalayas, and influenced anchialine caves at the edge of the ancient sea. The extensive new habitats provided opportunities for colonisation and rapid diversification. Future work should focus on testing the biological impact of the series of Tethyan changes.