Taking into consideration textual, material, and archaeological sources, this chapter offers an overview of the historical developments during the Persian imperial domination of Central Asia from the time of Cyrus II (ca. 600–530 bc) up to the events of 329–327 bc, when Alexander of Macedon’s invasion of the Persian Empire reached this vast region. This period is a key stage in the history and cultural shaping of Central Asia, but the severely restricted evidence available to us makes a precise reconstruction extremely difficult. Nevertheless, the chapter attempts a synthesis that highlights key historical processes and socioeconomic patterns and considers and interprets these in the light of the currently available evidence, especially on the basis of data from the most recent archaeological field research.