This study documents the history of epidemics in the ancient Near East, giving some examples from Mesopotamia, the Levant, and the Arabian Peninsula. It relies on the cuneiform scripts, the Sumerian and Akkadian languages and other inscriptions from the Levant, Old Testament texts and ancient Egyptian sources. These sources provide us with important information about epidemics that have spread across the Arab Mashreq since the third millennium BC, and how people and the state dealt with them. After presenting a general picture of epidemics and pandemics throughout history, the paper discusses the ancient period, then moves on to the “Plague of Justinian” (541-542 AD), known in Arab history and the Levant through its historical continuity with the plague of Amwas.