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The warm Pliocene epoch (5–3 million years ago) is often cited as a good analog for the near future climate because of its striking resemblance to the predictions of the “Intergovernmental Panel on Climate Change” for the next decades. Indeed, relative to today, during the Pliocene epoch, surface temperatures were 3–4°C warmer, sea level was about 5–40 meters higher, atmospheric CO2 concentrationswere relatively similar or slightly higher (~400 ± 50 ppmv), and ice sheets were restrained to Antarctica. However, since 3.0 Ma ago, the Earth’s climate has undergone a major transition from a warm and relatively stable state towards cold conditions marked by amplified glacial/interglacial cycles and widespread ice sheets in the Northern Hemisphere (NHG), and to a lesser extent over Antarctica. The causes and consequences of this global climate transition—driving warm periods to “icehouse” conditions marked by “Quaternary-style” glacial/interglacial cycles—are still uncertain. Yet, they may include the interaction of several mechanisms tied to oceanic and atmospheric circulations, tectonic-, greenhouse gases-, and biological activity, biogeochemical processes, and changes in Earth’s orbit.