HOX genes are transcription factors that are essential for the proper development of the müllerian tract in the embryonic period. It has been discovered that HOX genes are expressed in the adult uterus. Two of them, Hoxa10 and Hoxa11, have been demonstrated to be necessary for uterine receptivity and implantation in mice. Recent evidence also suggests such a role for HOX genes in humans. They are likely to be essential regulators of endometrial development in preparation for implantation. This article reviews the role of the HOX genes in the reproductive tract, their patterns of expression and regulation, the outcome of deficient HOX gene expression, and their potential mechanisms of action. The process of implantation is complex, and many molecular markers have been found expressed at high levels in the endometrium in the peri-implantation window. Targeted disruption has revealed that most of these molecules are redundant and not essential for implantation. The importance of Hox genes in this process has been well documented, and they remain one of the few well-characterized molecules necessary for implantation.