Implantation is a complex event requiring synchronization between a developing embryo and receptive endometrium. This process is governed by molecular mechanism mediated by homeobox (Hox) genes, which encode transcription factors. These factors guide embryologic development as well as regulate differential gene expression within the endometrium with each menstrual cycle. Spatiotemporal aberrations in HOX gene expression as seen with polycystic ovarian syndrome, endometriosis, hydrosalpinges, and endocrine disrupters compromise implantation. The role of HOX genes and their products continues to be explored as animal models that demonstrate implantation-specific infertile phenotypes continue to be investigated.