In this paper I will analyse the different features of the Pleiades in the astronomical, astrological, and calendrical interpretation as well as their mythical and cultural background in ancient Mesopotamia. According to cuneiform sources, the Pleiades are among the most important stars. They are simply known in Sumerian as ―the Stars‖ (MUL.MUL), while their Akkadian name, ―the Bristle‖ (zappu), links them to the imagery and the cultural context of the ―Bull of Heaven‖ constellation (Taurus), to which they belong. Pleiades are frequently depicted as seven dots or seven stars, and identified on a mythological level with groups of seven divine beings. In fact, the Sumerian ideogram for ―seven‖ is used as an alternative name for the Pleiades. In particular they show a close relation to a group of demons, called the Seven (Sebēttu), that, according to an etiological myth, causes the eclipse of the moon. The relation of the Pleiades to the war and death sphere is strengthened by their association with the Netherworld god Nergal/Erra, as well as their identification with the god’s planet (Mars). Finally, the Pleiades are among the few celestial bodies that receive a cult, and specific prayers are dedicated to them. From the sources it emerges that the Pleiades are mainly related to the movement of the Moon, and it is worth noting that the list of constellations of the ecliptic begins precisely with the Pleiades. Furthermore, the Pleiades play an important part in the calendrical reckoning, a role that is clearly stated in almanacs as the MUL.APIN, as well as in the intercalation scheme based on the conjunction of the Moon and the Pleiades.