This presentation provides an overview of the evidence for and the methodological issues surrounding ancient Mesopotamian prayer, with an emphasis on the Akkadian material. Some of the questions pursued in this talk include: How does one determine what counts as a prayer in Mesopotamia? What physical and verbal activities might be included when Mesopotamians prayed? As our evidence is textual in nature, how do we reconstruct the text of prayers from broken tablets and deal with textual diversity when a prayer is preserved on multiple and differing manuscripts? What are the various genres of prayer attested among the evidence? Why were prayers considered efficacious and what made them so or hindered them from being so? The final third of the paper will be given to an exploration of two prayers from about a thousand years apart. One is an Old Babylonian letter-prayer. The other is an incantation-prayer from the mid-first millennium.