We describe an episode of mass poisoning during the ancient Third Mithridatic War. In a brutal and well-planned ambush, forces from the Kingdom of Pontus destroyed a Roman column through the clever use of “mad honey.” Incapacitated by the acute poisoning, the Romans were unable to hold off the Pontic forces. We conclude that the debilitating symptoms that the Roman soldiers experienced were due to the presence of grayanotoxins in the honey. Although they were likely self-limiting, developing these symptoms in an enemy ambush made a lethal combination. The “mad honey” environmental threat continues to persist in the Black Sea region to this day and is an etiology that modern physicians should be aware of.