Reproduction in mammals is a highly complex biological process. The critical importance of reproduction to propagation of species required the natural evolution of various strategies that vary considerably across species. Regardless of species, a dialogue between the developing conceptus (embryo-fetus and associated placental membranes) and maternal uterus must be established during the peri-implantation period. The uterus must provide a microenvironment that supports growth and development of the conceptus and is receptive to implantation. During the same period, the conceptus must provide its pregnancy recognition signaling to sustain the functional life of corpora lutea for production of progesterone which is essential for implantation and placentation; critical events for successful pregnancy. However, it is within the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or to the failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. The challenge is to understand the complexity of key mechanisms that are characteristic of successful reproduction in humans and animals and to use that knowledge to enhance fertility and reproductive health or to establish acceptable methods for control of fertility.