Implantation is a complex developmental process that involves an intimate "cross-talk" between the embryo and uterus. Synchronized development of the embryo to the blastocyst stage and differentiation of the uterus to the receptive state are essential to this process. Successful execution of the events of implantation involves participation of steroid hormones, locally derived growth factors, cytokines, transcription factors and lipid mediators. Using gene-targeted mice and a delayed implantation model, our laboratory has been exploring potential interactions among steroid hormones, growth factors, cytokines and prostaglandins in this process. This review article highlights some of our recent observations on the roles of estrogen, catecholestrogen, the EGF family of growth factors, leukemia inhibitory factor and cyclooxygenase-2 derived prostaglandins and their interactions in embryo-uterine "cross-talk" during implantation.