Since the rise of the first urban centers, the Middle Euphrates has functioned as a routeway between Mesopotamia and Syria. The towns and caravanseri located along the river served as important conduits of international exchange and as frontier towns buffering larger empires to the east and west. My research has investigated one small district along the Middle Euphrates. I have tried to document not only site distribution but also levels of communication between the middle valley of Euphrates and the southern Mesopotamian and western Syria core areas. Site distribution patterns show over and over again the location of entrepots, staging posts, and forts in this district. The chronological span of this study extends from ca 10,000 B.C. to A.D. 1980, an identifiable longue duree in which recurring cycles of conquest, depopulation, and revivification can be discerned. The area appears to have fared best during periods of intense competition among rival states for access to long-distance trade routes. However, when interactions between rival states in the stronger core areas of Syria and Mesopotamia resulted in the formation of empires whose capitals and interests lay far from the Middle Euphrates, the towns of this region perished. Nevertheless, the capture of the Middle Euphrates appears to have always been an important strategic battle in expansionistic efforts of such empires. I have analyzed the spatial distribution of sites in this region using data from a multi-stage field program. This program combined data from reconnaissance survey, intensive surface survey, intensive jeep survey, and test excavations at the Uruk period site of Tall Qraya with information from the broad-scale excavations at the regional center at Tall Harīrī and the provincial center at Tall al 'Ashārah. It is only with such archaeological data of long time depth gathered from many sources, in combination with information from textual sources, that one can attempt a "total history" of this area.