The Müllerian duct (MD) forms the female reproductive tract (FRT) consisting of the oviducts, uterus, cervix, and upper vagina. FRT function is vital to fertility, providing the site of fertilization, embryo implantation and fetal development. Developmental defects in the formation and diseases of the FRT, including cancer and endometriosis, are prevalent in humans and can result in infertility and death. Furthermore, because the MDs are initially formed regardless of genotypic sex, mesenchymal to epithelial signaling is required in males to mediate MD regression and prevents the development of MD-derived organs. In males, defects in MD regression result in the retention of FRT organs and have been described in several human syndromes. Although to date not reported in humans, ectopic activation of MD regression signaling components in females can result in aplasia of the FRT. Clearly, MD development is important to human health; however, the molecular mechanisms remain largely undetermined. Molecular genetics studies of human diseases and mouse models have provided new insights into molecular signaling during MD development, regression and differentiation. This review will provide an overview of MD development and important genes and signaling mechanisms involved.

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