Lake isotope records can be used to assess the spatial coherency of Late Quaternary climate change across the circum-Mediterranean region. We place modern and palaeo-data within a simple conceptual lake response model to show that the isotope hydrology of most Mediterranean lakes has been influenced strongly by water balance, even in those systems that are chemically dilute (i.e. freshwater). δ18O data on biogenic and endogenic carbonates from 24 lake basins are used to reconstruct multi-millennial-scale trends since the LGM. While it is difficult to make direct comparisons between lake records in terms of single climatic parameters, coherent regional isotopic trends can be identified. During glacial times Mediterranean lakes deposited carbonates isotopically heavier in δ18O compared to the Holocene, partly due to source area effects. Isotopic enrichment was most marked during intervals corresponding to the H1 and Younger Dryas events, confirming that Late Pleistocene cold stages in the North Atlantic region were marked by aridity around much of the Mediterranean. Almost all Mediterranean lake records shifted to more depleted isotopic values during the Last Glacial–Interglacial Transition (LGIT). This shift is the reverse of the trend which characterised the same transition in lakes from northern and central Europe, and suggests that temperature changes were not an important direct driver of Mediterranean lake isotopic records over glacial–interglacial timescales. In the early Holocene, many lakes in the eastern part of the region were more depleted isotopically than in recent millennia. This corresponds with marine sapropel formation, both chronologically and geographically, and implies that increases in local rainfall contributed significantly to the creation of a freshwater lid and anoxia in the East Mediterranean Sea. In contrast, no such pattern is currently apparent from lake isotope records from the West Mediterranean, suggesting a possible NW–SE contrast in climate history during the Holocene.