Tissue factor (TF), is a transmembrane protein whose role was first identified as that of the initiator of hemostasis via a series of complicated protein cascades. It is now known however, that TF participates in angiogenesis as well as several processes that contribute to disease progression. Over the last 20 years, our laboratory has studied the expression and function of this molecule in both the pregnant and non-pregnant human endometrium. We demonstrated that TF is particularly upregulated at the time of implantation making it a critical factor to protect against excessive bleeding during trophoblast invasion. We have subsequently demonstrated the altered expression of this factor after long term contraception as well as in endometriosis. We proposed that any changes in this well regulated process can result in various pathologies of the endometrium including, infertility, bleeding, endometriosis, preeclampsia, preterm labor or thrombosis. Below we describe the latest findings of the expression and function of TF as well as its specific role in physiologic or pathologic conditions of the human endometrium.