The Late Neogene witnessed various major paleoceanographic changes that culminated in intense Northern Hemisphere Glaciation (NHG). The cause and effects of these changes are still debated. We use a multiproxy approach to determine the relative timing of the closure of the Panama gateway, changes in Atlantic circulation, global cooling and ice sheet growth. Benthic foraminiferal Mg/Ca records from a Pacific and an Atlantic Site have been produced and are interpreted in terms of bottom water temperatures. These Mg-temperature records are combined with published benthic d13C, N18O and erosion records to reconstruct the flow of proto-North Atlantic Deep Water (proto-NADW) over the past 12 Ma. The results suggest that between 12.5and 10.5 Ma, and again between about 8.5 and 6 Ma, a nutrient-depleted water mass that was colder (by 1-2˚C) and fresher than the intervening deep water mass filled the Atlantic basin. This proto-NADW became warmer (by ~1˚C) and saltier between 6 and 5Ma, coincident with the restriction of surface water flow through the Central American Seaway. The Mg-temperature records define a subsequent global cooling trend of~3.5˚C between 5 Ma and today. Early NHG in the late Miocene was perhaps related to the formation of the relatively cold, fresh proto-NADW. The formation of the warmer and saltier proto-NADW in the early Pliocene may have initially limited Northern Hemisphere ice growth. However, the increased moisture released at high northern latitudes associated with formation of 'warm' proto-NADW, coupled with the global temperature decrease of deep (and hence polar surface) waters, likely helped initiate the intense NHG of the Plio-Pleistocene.