The human endometrium is receptive for implantation of a blastocyst for only 4–5 days in each menstrual cycle. Failure of implantation is a major reason for infertility in women and the inability to achieve endometrial receptivity is responsible for much of the failure of reproductive technologies. Endometrial receptivity requires changes in the uterine luminal and glandular cells, particularly in terms of their secretory capacity and altered expression of adhesion molecules. In parallel with these changes, decidualisation (differentiation) of the endometrial stroma is initiated in women during the receptive phase, regardless of the presence of a blastocyst. Increased leucocyte numbers are also important. The microenvironments provided by the endometrium during the receptive phase and that support implantation are highly complex and constantly changing as implantation progresses. The present review provides a comprehensive overview of the cellular and molecular events of human implantation. It also summarises work from our laboratories emphasising the functional importance of proprotein convertase 6, along with key cytokines (interleukin-11, leukaemia inhibitory factor, activin A) and chemokines (including CX3CL1 and CCL14), during implantation. Of particular importance is how these mediators contribute to receptivity and how they are disturbed in infertile women. Factors that are critical for uterine receptivity may also be manipulated to provide new contraceptive strategies for women.