The interval from the middle Eocene to early Oligocene represents one of the most significant transitions in Earth’s climate, during which greenhouse conditions were supplanted by icehouse conditions of the present day. This global transition was preceded by a long-term cooling phase and short-term uncorrelated variations in several marine proxies, which indicate paleoceanographic instabilities prior to the key climatic transition. We integrate previous multidisciplinary studies with recent data from the Massignano section (Umbria-Marche Basin) and summarize interpretations of studies from the past 20 yr that have been based on the Eocene-Oligocene boundary global stratotype section and point (GSSP). Based on the many data sets from this section, with an emphasis on the rock magnetic data, we propose that the fluctuations and final cessation of a westward subtropical Eocene Neotethys (STENT) current were drivers in the climatic transition from greenhouse to icehouse conditions. Our hypothesis considers that the global variable climatic conditions were synchronous to large changes in circulation in the western Neotethys Ocean, which were primarily due to paleogeographic and sea-level changes. Specifically, the closing of the gateway between the Arabian and Eurasian plates, through coupling of sea-level changes, could represent the threshold or one of the triggers that caused the paleoceanographic variations in the Neotethys and in global ocean circulation patterns during the end of the Eocene.