Estradiol is a steroid hormone that regulates the structure and function of the female reproductive system. In addition to its genomic effects, which are mediated by activated nuclear receptors, estradiol elicits a variety of rapid signaling events independently of transcriptional or genomic regulation. These nongenomic actions influence the milieu of the genital tract, which changes the ability of pathogens to infect the genital tract. This review discusses our current knowledge regarding the mechanisms and relevance of nongenomic estradiol signaling in the genital tract that could change the ability of pathogens to invade epithelial cells. PubMed was searched through January 1980 for papers related to estradiol actions in the ovary, fallopian tube, uterus and cervix. The mechanisms conveying these rapid effects consist of a multitude of signaling molecules and include cross-talk with slower transcriptional actions. The nongenomic actions of estradiol that influence the infectious abilities of pathogens occur either directly on the genital tract cells or indirectly by modulating the local and systemic immune systems. Additional in-depth characterization of the response is required before the normal and pathological reproductive functions of the nongenomic estradiol pathway can be targeted for pharmacological intervention. © 2013 Solar and Velasquez; licensee BioMed Central Ltd.