The story of the political, social, and military relation of Rome with the Arabs in the region goes back, as far as the textual records testify, to the time of Claudius. This chapter focuses on the discussion in the period in which the territories of North Mesopotamia were more or less consistently included within the limits of the empire, roughly between the early 2nd c. ce and the 4th c. ce. A different discourse needs to be done about the presence of Arab communities, often confounded with contemporary nomadic groups. The chapter seeks to demonstrate how the complex social and geographical background of the region also generated non-linear interactions. Relationships of power and alliances fluctuated, and the in between the empires parts played a major role in this. The identification of North Mesopotamia and part of central Babylonia as an “Arab land” is also shared by other sources such as Xenophon and Pliny.