Successful implantation requires synchronous development of embryo and endometrium. Endometrial receptivity results from progesterone-induced differentiation of endometrial cells, generally achieved during the mid-secretory phase of the cycle. Failure to properly develop receptivity results in failed or inadequate implantation and hence no ongoing pregnancy. The blastocyst undergoes final development, apposition, attachment and initiates invasion of the endometrial epithelium within the uterine cavity. Thus, the microenvironment provided by uterine fluid, particularly glandular secretions, is essential for implantation. Analysis of endometrial fluid has identified cytokines, chemokines, proteases, antiproteases and other factors that modulate blastocyst functions relevant to implantation. Exosomes/microvesicular bodies released from the endometrium (and likely also the embryo) are present in uterine fluid. These can transfer miRNA, proteins and lipids between cells, thus providing endometrial–embryo communication in the peri-implantation period. Understanding the uterine microenvironment, and its effects on endometrial–embryo interactions, will provide opportunities to modify current infertility treatments to improve success rates.