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The Hellenistic period (4th - 1st c. BC), if the figures of Alexander the Great and Cleopatra are excluded, is relatively less known among the Greek eras. It's often considered a period of transition, sometimes even of decline or decadence, between the brilliance of the Greek Classical Era and the strength of the Roman Empire. However, the splendor of cities, such as Alexandria, Antioch, Pergamon, the importance of foreign trade, cultural exchanges, and the dominant role of Greek and its diffusion profoundly affected the face of the ancient Middle East later under Roman dominion.

The Hellenistic era was defined by 19th century historians (the term "hellenistic" was first used by the German Historian Johann Gustav Droysen in Geschichte des Hellenismus in 1836 and 1843) as part of a linguistic and cultural criterion for the spectacular increase in the areas where Greek (ἑλληνίζειν / hellênízein) was spoken, and therefore a term for the phenomenal expansion of Hellenism. However, according to Paul Veyne, the phenomena of Hellenization of large regions and of the meeting of ancient Eastern and Western civilizations continued under the "Greco-Roman Empire." The chronological limits of the Hellenistic period are therefore conventional and political: the era begins with the conquests of Alexander the Great and ends when the suicide of the last great Hellenistic ruler, Queen Cleopatra VII of Egypt, led to the Roman conquest of Egypt.

Recent archaeological and historical work has lead to a reevaluation of the period, especially two specific aspects of it: the existence and stature of great kingdoms lead by dynasties of Greek origin (Ptolemaic, Seleucid, Antigonid, Attalid, etc.) and the role of hundreds of cities whose importance, contrary to a long pervasive idea, was far from declining.

The conquests of Alexander
King of Macedon at 20 years old, master of Greece two years later, Alexander the Great then began his brief reign — barely 13 years between 336 and 323 BC — the quickest and most spectacular conquest of Antiquity. A kingdom that was all in all average, associated with a few Greek cities, was able to defeat the greatest empire of the time period, the Persian Empire of Darius III. The Achaemenid dynasty was conquered in four years (334-330) and in three battles, those of the Granicus, Issus, and Gaugamela. The following three years, until 328, were devoted to the slow and difficult conquest of the Satraps in Central Asia and subsequently, until 325 to assuring the Macedonian domination of parts of northwest India. It was there that Alexander, under pressure of depleted troops, was forced to stop pursuing his expansion and returned to what had become the heart of his empire, Mesopotamia.

In order to ensure the longevity of his power, he entrusted the ruling class of the former Achaemenid Empire with filling the administrative skeleton of his kingdom. He further attempted to create a monarchy bearing both a heritage that was in part Greek but also Persian and, more generally, Asiatic. The brutal death of the king, probably due to illness, at only 33 ended this original attempt, which had been acutely contested by his Macedonian entourage.