The endometrium undergoes an ordered process of differentiation leading to receptivity to embryonic implantation. HOX genes direct this development in a fashion similar to that in which they direct embryonic development, including development of the reproductive tract. HOXA10 and HOXA11 expression increases during the menstrual cycle, increasing drastically in the midluteal phase, at the time of implantation. This expression is regulated by sex steroid hormones. This expression is necessary for implantation of the blastocyst as demonstrated by the decreased implantation rates in women with altered HOX expression. HOX genes are markers of endometrial receptivity. The possibility of augmenting HOX gene expression with gene therapy to improve implantation has promise for the future.