Significant new information shows that the Campanian Ignimbrite (CI) eruption from the Phlegrean Fields, southern Italy, was much larger than hitherto supposed and in fact one of the largest late Quaternary explosive events. The eruption can be dated to 40,000 calendar years ago, within the interval of the so-called Middle to Upper Paleolithic 'transition'. Its position can be precisely correlated with a number of other environmental events, including Heinrich Event 4 (HE4), the Laschamp excursion, and a particular cosmogenic nuclide peak. In view of this unique combination of factors, we studied the CI volcanic catastrophe with particular attention to its impact on climate and human ecosystems, including potential interference with ongoing processes of cultural evolution (biological evolution is best left aside for the moment). The contribution of this research is chronological and ecological. The CI volcanic event provides an unequalled means of correlating stratigraphic sequences across Western Eurasia, either directly or indirectly, and affords a unique opportunity to establish the age and climatic context of important archaeological sequences. Ecologically, the CI eruption inevitably interacted with the beginning of HE4 in terms of atmospheric feedback systems. Their combined forcing produced a sudden and at least hemispheric climatic deterioration; a 'volcanic winter' scenario cannot be ruled out. Paleolithic occupation was severely altered throughout the direct-impact zone of the eruption and likely along fringe areas in southern and southeastern Europe. The above observations call for a reconsideration of the processes and rhythms involved in the Middle to Upper Paleolithic 'transition'. A tentative model is suggested that links the exceptional environmental stress at 40,000 BP with processes already active in Paleolithic societies, leading to a period of accelerated change in cultural configurations. These eventually evolved into an Upper Paleolithic proper at a later date. The evidence to invoke allochthonous cultural input or invasionist scenarios is not considered compelling.