Climate variability during the present interglacial, the Holocene, has been rather smooth in comparison with the last glacial. Nevertheless, there were some rather abrupt climate changes. One of these changes, the desertification of the Saharan and Arabian region some 4–6 thousand years ago, was presumably quite important for human society. It could have been the stimulus leading to the foundation of civilizations along the Nile, Euphrat and Tigris rivers. Here we argue that Saharan and Arabian desertification was triggered by subtle variations in the Earth's orbit which were strongly amplified by atmosphere- vegetation feedbacks in the subtropics. The timing of this transition, however, was mainly governed by a global interplay between atmosphere, ocean, sea ice, and vegetation.