A mid- to late-Holocene synthesis of fire activity from the Mediterranean basin explores the linkages among fire, climate variability and seasonality through several climatic and ecological transitions. Regional fire histories were created from 36 radiocarbon-dated sedimentary charcoal records, available from the Global Charcoal Database. During the mid-Holocene ‘Thermal Maximum’ around 7500—4500 cal. BP, charcoal records from the northern Mediterranean suggest an increase in fire while records from the southern Mediterranean indicate a decrease associated with wetter-than-present summers. A North—South partition between 40° and 43°N latitude is apparent in the central and western Mediterranean. Relatively abrupt changes in fire activity are observed c. 5500—5000 cal. BP. Records of Holocene fire activity appear sensitive to both orbitally forced climate changes and shorter-lived excursions which may be related to North Atlantic cold events, possibly modulated by an NAO-like climate mechanism. In cases where human—fire interactions have been documented, the regional coherency between fire occurrence and climate forcing suggests a dominant fire—climate relationship during the early—mid Holocene. The human influence on regional fire activity became increasingly important after c. 4000—3000 cal. BP. Results also suggest that: (1) teleconnections between the Mediterranean area and other climatic regions, in particular the North Atlantic and the low latitudes monsoon areas, influenced past fire activity; (2) gradual forcing, such as changes in orbital parameters, may have triggered abrupt shifts in fire activity; (3) regional fire reconstructions contradict former notions of a gradual (mid- to late-Holocene) aridification of the entire region due to climate and/or human activities and the importance of shorter-term events; (4) Mediterranean fire activity appears hightly sensitive to climate dynamics and thus could be considerably impacted by future climate changes.