An emerging concept in female reproduction is the role of endocannabinoids, a group of endogenously produced lipid mediators that bind to and activate cannabinoid receptors. Although adverse effects of cannabinoids in female reproduction have been implicated for years, the mechanisms by which they exert these effects remained elusive. With the identification of cannabinoid receptors, endocannabinoid ligands, their key synthetic and hydrolytic pathways, and the generation of knockout mouse models for cannabinoid receptors, a wealth of information is now available regarding the significance of cannabinoid/endocannabinoid signaling in early pregnancy. This review focuses on various aspects of endocannabinoid signaling in preimplantation embryo development and activation, and uterine differentiation during the periimplantation embryo-uterine dialog. It is hoped that a deeper understanding will lead to potential clinical applications of the endocannabinoid system as a target for regulating female fertility.