The innate immune responses at mucosal surfaces of the lower female genital tract play a central role in preventing the establishment of infection. Variability in the genes regulating innate immune recognition or response to infectious microorganisms could explain interindividual differences in susceptibility to infection and severity of infectious disorders. Of the numerous genetic variations identified within immunoregulatory genes, only a few have so far been studied in relation to infectious disorders of the lower female genital tract. Although these studies broaden our understanding of the genetic influence on mucosal innate immunity and microbiologic outcome, they also highlight the complexity of links between genotypical and phenotypical features, ie, the influence of a single genetic marker on the phenotype is at best moderate and is not constant in every ethnic/racial group. Such inconsistency is primarily attributed to gene-to-gene interactions and demographic genetic variability. Large case-control studies evaluating multiple genetic markers simultaneously in well-defined subgroups will characterize patients more accurately and pave the way to personalized medicine.