Human embryo implantation requires an activated blastocyst, a receptive endometrium and communication between the two. Implantation is initiated following apposition and firm adhesion to the endometrium where abnormalities in firm adhesion results in implantation failure and infertility. Abnormal implantation can result in disease associated with placental insufficiency. Very little is known of blastocyst-endometrial interactions in humans. Recently non-coding RNA have been identified to be dysregulated in implantation disorders including implantation failure/infertility and miscarriage and preeclampsia suggesting they may be useful as biomarkers and treatments for these conditions. Using a unique model to study human embryo – endometrial interactions we demonstrate that cellular and extracellular non-coding RNA regulate embryo implantation. We also demonstrate that microRNA processing machinery in the endometrium is abnormal during receptivity in women with unexplained infertility implying an important role in the endometrial tissue preparation for implantation. As each microRNA has the ability to alter the levels of many genes and proteins they are master regulators and may be useful as treatment targets for disorders of implantation.