HOX genes are transcriptional regulators that play an essential role in determining tissue identity during embryonic development. HOX genes are involved in the development of the Müllerian system and then continue to be expressed in the adult uterus. Two HOX genes have been demonstrated necessary for uterine receptivity in knock-out mice. We have recently elucidated the expression patterns and regulation of HOX genes in the development of the human endometrium during the menstrual cycle. HOX genes are likely key regulators of human implantation. This paper will review the role of HOX genes in the reproductive tract, specifically the evidence that HOX genes are important for human endometrial development and receptivity.