The myth of Perseus and Andromeda has endured since antiquity as one of the best known and most popular myths in Western culture. Watkins, who examines the Indo-European roots of the dragon-slayer topos, relates it to similar myths from Indian, Persian, and Mesopotamian literary sources, and traces its roots to an earlier, perhaps pre-literary era. Although this myth is indeed typical of the dragon-slayer topos, every culture has emphasized different aspects of it. The myth of Perseus and Medusa also has roots that can be traced back to the third millennium BCE, and is considered by many scholars to have developed from the monstrous Mesopotamian Humbaba, who has a similarly terrifying appearance and a deadly gaze. This chapter examines artistic and literary renditions of these two myths in the context of Greco-Roman culture, and contrasts them with one another. Examining the same hero in two contrasting scenarios involving a woman and a dragon allows for an exploration of the complex meanings of the interactions between them. As the following discussion will show, artistic representations of these myths depict a wide range of symbolic attributes, which were transformed over time in reaction to cultural changes, thus reflecting the gravitation to different sites of meaning.