Blastocyst implantation into the endometrium is critical for the establishment of pregnancy and is tightly regulated by factors within the blastocyst-endometrial micro-environment. Implantation is a continuum involving blastocyst adhesion to the endometrial epithelium followed by trophoblast penetration of the epithelium. The trophoblast proliferates and invades through the endometrium, with a subpopulation acting to remodel the spiral arteries. Trophoblast-endometrial interactions in humans involve carefully orchestrated temporal and spatial alterations in factors that are critical for pregnancy success. Emerging evidence suggests important roles for locally produced cytokines including interleukin 11 and leukemia inhibitory factor in the various stages of implantation. This review focuses on the role of these cytokines in trophoblast-endometrial interactions during the establishment of human pregnancy.