AbstractAs a critical stage of pregnancy, the implantation of blastocysts into the endometrium is a progressive, excessively regulated local tissue remodeling step involving a complex sequence of genetic and cellular interplay executed within an optimal time frame. For better understanding the causes of infertility and, more importantly, for developing powerful strategies for successful implantations and combating infertility, an increasing number of recent studies have been focused on the identification and study of newly described substances in the reproductive tree. The endothelins (ET), a 21‐aminoacidic family of genes, have been reported to be responsible for the contraction of vascular and nonvascular smooth muscles, including the smooth muscles of the uterus. Therefore, this review aims to comprehensively discuss the physiological role of endothelins and signaling through their receptors, as well as their probable involvement in the implantation process.