Introduction: With IVF results now showing good evidence of having reached a steady plateau  despite the introduction of impressive new laboratory techniques aimed at selecting the embryo most likely to implant, attention is increasingly turning to the other key determining factor of successful implantation: the endometrium. The uterine factor in implantation has long been considered to be minor, but as the impact of further advances in embryology appears likely to remain incremental at best, clinicians, scientists, and biotech companies are focusing on the maternal side of the implantation equation. The concept of clinical manipulation of endometrial receptivity in infertility is not new. Many patients are offered a “smorgasbord” of adjuvant therapies aimed at improving the chance of the transferred embryo successfully implanting, but the clinical impact of these largely empirical therapies has thus far been disappointing. Perhaps it is time therefore to consider the endometrium in a different way. The paradigm of the endometrium as an essentially passive partner in implantation has gained currency with the growth of embryology and the impressive gains made in culture, freezing, and selection techniques. This reductionist view of the endometrium has gained support from results of oocyte donation programs, in which good outcomes are reported in women who failed to conceive with their own eggs. The assumption that this indicates that only embryo quality is the determining factor ignores the more hormonally physiological environment into which embryos derived from donor eggs are placed. Indeed, the excellent results now being achieved with frozen embryo thaw cycles, where embryos are transferred into an unstimulated endometrium, are being widely attributed to this factor. However, the intra-uterine environment is now being recognized as a key factor, not only in determining successful implantation, but in the nutrition and programming of the peri-implantation embryo. These new insights are providing novel opportunities for therapeutic and indeed nutritional interventions aimed at optimizing the peri-conceptional milieu. It is time to re-evaluate the endometrium as a more active partner in implantation. In this chapter, recent advances in our understanding of the dynamic biosensor and supportive role played by the endometrium will be outlined, and preconceptional interventions aimed at improving endometrial function will be reviewed. Finally, novel strategies for modifying preconceptional behaviors will be introduced.