This study examines how the Serpent Column in Constantinople came to be recognized as a talisman against snakes and snakebites in the 1390s. It first gives a working definition of what a talisman was in Byzantium. It shows that, despite the co-existence of different ideas of what talismans were, they share the basic principle that the talisman acts within a broader network of non-human forces and entities. Second, it shows how contemporaries used this understanding of talismans when they began to recognize the Serpent Column as a talisman.