The biotic and geologic dynamics of the Great American Biotic Interchange are reviewed and revised. Information on the Marine Isotope Stage chronology, sea level changes as well as Pliocene and Pleistocene vegetation changes in Central and northern South America add to a discussion of the role of climate in facilitating trans-isthmian exchanges. Trans-isthmian land mammal exchanges during the Pleistocene glacial intervals appear to have been promoted by the development of diverse non-tropical ecologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10914-010-9144-8) contains supplementary material, which is available to authorized users.