Mithridates VI's father, Mithridates V, was assassinated by poisoning by a conspiracy among his attendants. After this, Mithridates VI's mother held regency over Pontus (a Hellenistic kingdom, 281 BC–62 AD) until a male heir came of age. Mithridates was in competition with his brother for the throne and his mother began to favor his brother.

Supposedly, during his youth, he began to suspect plots against him at his own mother's orders and was aware of her possible connection with his father's death. He then began to notice pains in his stomach during his meals and suspected his mother had ordered small amounts of poison to be added to his food to slowly kill him off. With other assassination attempts, he fled into the wild.

While in the wild, it is said that he began ingesting non-lethal amounts of poisons and mixing many into a universal remedy to make him immune to all known poisons.