For many years it was thought that the female reproductive tract was a sterile environment, devoid of immune cells or pathogens. We now know that the immune system represents an important component of reproductive tissues, influencing many of its biological functions. Similarly, bacteria are present within the female reproductive tract as a normal component. Therefore, the female reproductive tract must promote a certain level of host protection against pathogens whilst maintaining commensal flora, in addition to facilitating normal menstrual cycling, successful fertilization and implantation. Furthermore, during pregnancy, the human endometrium becomes an immunologically unique site that again, must maintain host defense against an array of microbial pathogens, but must also sustain the semiallogeneic fetus and placenta. In addition to the cells of the immune system, the mucosal epithelium of the female reproductive tract, as well as tissues of the maternal-fetal interface, may actively participate in the control of pathogens, however, the precise mechanisms by which this occurs are poorly understood. Toll-like receptors (TLR) are key components of the innate immune system which recognize conserved sequences on the surface of microorganisms and trigger effector cell functions. We and others have shown the expression of Toll-like receptors in epithelial cells of female reproductive tissues and at the maternal-fetal interface, suggesting that these specialized cells can recognize and respond to the presence of microorganisms and coordinate an immune response. Clinical studies have shown a strong association between intrauterine infections and fertility problems as well as certain pregnancy complications. Therefore, innate immune responses within the female reproductive tract against microorganisms may have a significant impact on implantation and on the success of a pregnancy. This review will discuss the role of Toll-like receptors in the normal cycling female reproductive tract and at the maternal-fetal interface during pregnancy.