This paper explores the impact of major glacial/interglacial paleohydrologic variations in the Middle-Paleolithic Levant on hominin migration and occupation. The climatic reconstruction is based primarily on the most straight-forward paleohydrologic records recently published. These terrestrial proxies convey direct paleoenvironmental signals of effective precipitation and aquifer recharge. The two main proxies are temporal changes of terminal lake levels in the Dead Sea basin and periods of deposition or non-deposition of speleothems. Other records, such as stable isotopes, if interpreted correctly, correspond well with these two direct proxies. All the records consistently indicate that the last two glacial periods in the central Levant were generally wet and cool, while the last two interglacials were dry and warm, so more water was available for the ecosystem and thus hominins during glacial periods than during interglacials. Some proxies indicate that the higher precipitation/evaporation ratio during glacial periods involved higher precipitation rather than only reduced evaporation. Beyond the general mean glacial/interglacial climate suggested here, variations occurred at all temporal scales throughout glacial or interglacial periods. In the Sahara-Negev arid barrier, moister conditions occurred during Marine Isotope Stage (MIS) 6a-5e, when Anatomically Modern Humans apparently migrated out of Africa. We suggest that this migration, as well as the later Neanderthal expansion from Southeast Europe or the Anatolian plateau into the Levant during early MIS 4, could be facilitated by the observed major climatic variations.