The female reproductive tract is a unique mucosal environment that is exposed to and interacts with a variety of antigens, including commensal bacteria, potentially pathogenic microbes as well as sperm and semen. The upper part of the tract, primarily endometrium, has the principal function of providing a supportive environment to allow implantation and growth of a semiallogeneic fetus. To fulfill these divergent functions, the immune system in the female reproductive tract (FRT) has developed a number of adaptations, under the influence of the female sex hormones, estradiol and progesterone. The innate immune system in the FRT consists of a full repertoire of immune cells and a number of soluble factors, including mucus, antimicrobial peptides, and interferons that block infections directly or indirectly. The innate cells in the FRT include NK cells, macrophages and DCs, neutrophils, and innate lymphocytes, as well as the tissue epithelial cells, that are responsible for the first line of defense against pathogens. They also initiate pathogen-specific and memory T cell and B cell–mediated adaptive immune responses. Viral infections in the FRT induce both innate and adaptive immune responses that can control the severity and clinical manifestation of the primary infection as well as form long-term antiviral immunity that can render future reactivations asymptomatic. Both the innate and adaptive immune responses in the female genital tract are under the complex regulation of female sex hormones during the different phases of menstrual cycle, pregnancy, and following hormonal contraceptive use.