The shift from "Hellenic" to "Hellenistic" in the history of the Mediterranean world represents the shift from a culture dominated by ethnic Greeks, however scattered geographically, to a culture dominated by Greek-speakers of whatever ethnicity, and from the political dominance of the city-state to that of larger monarchies. In this period the traditional Greek culture is changed by strong Eastern, especially Persian, influences.

Modern historians see the death of Alexander the Great in 323 BC as dividing the Hellenic period from the Hellenistic. Alexander and the Macedonians conquered the eastern Mediterranean, Mesopotamia, and the Iranian plateau, and invaded India; his successors held on to the territory west of the Tigris for some time and controlled the eastern Mediterranean until the Roman Republic took control in the 2nd and 1st centuries BC. Most of the east was eventually overrun by the Parthians.

Following Alexander's death, there was a struggle for the succession, known as the wars of the Diadochi (Greek, "successors"). These ended in 281 BC with the establishment of three large territorial states: