Roman activity in Egypt’s Eastern Desert fluctuated significantly, ranging from intense exploitation of its resources and desert routes that facilitated Indo-Mediterranean trade, to the Roman Empire’s near total abandonment of the region. In those areas crucial to the Roman state – stone quarries, Red Sea ports, desert road stations and mining settlements – a nadir in occupation occurs near the mid-third century CE. But archaeological evidence indicates that significant reductions in activity occurred between the late second and early third centuries CE – i.e., in the Antonine and Severan Periods. The downturn was probably a result of distant geopolitical engagements, outbreaks of disease and/or shifting patterns of trade, which led to the Empire’s neglect of and gradual withdrawal from the area. This article reviews the archaeology of the Eastern Desert and considers the reason(s) this once-important region fell into decline. [Formula: see text]