Implantation involves complex molecular interactions between implanting blastocysts and the hormonally primed uterus. Gene targeting allows the generation of mice lacking a specific gene or genes and has proved to be of considerable value when combined with classical physiology in understanding many biological questions, such as the process of implantation. In this article, we review genes that have been demonstrated by gene targeting in mice to be required in the uterus for implantation. In particular, we focus on a specific class of developmental control genes, the mammalian Hox genes, and their role in this process. Lastly, we attempt to synthesize current knowledge about the genetic control of implantation and to build a working genetic model for the implantation pathway.