Modern data of the relationship of various compositions of the vaginal microbiota, immune defense factors and susceptibility to viral infections: human immunodeficiency virus (HIV), human papillomavirus (HPV), genital herpes (HSV-2), are presented. Analysis of metagenomic studies of the vaginal microbiota composition and the relative abundance of bacterial species using the 16S rRNA gene sequencing was performed. 5 microbial communities and 5 types of vaginal microbiomes have been identified. The data of vaginal ecosystem, consisting of epithelial cells, microbiota, cells of innate and adaptive immunity, and their influence on the susceptibility to infection with a number of sexually transmitted infections are presented. Changes in immune and epithelial homeostasis caused by the production of proinflammatory cytokines and chemokines lead to an increase in the recruitment of immune cells, and decrease in the viscosity of cervico-vaginal fluid through the production of sialidase, α-fucosidase, α- and β-galactosidase, N-acetylglucosaminidase. Consequently, these changes of the vaginal ecosystem affect the barrier properties of cervico-vaginal fluid, genital epithelium and increase the risk of infection with sexually transmitted pathogens. IV type of vaginal microbiota most strongly increases the risk of infection with HIV, HPV, HSV-2, a number of other sexually transmitted infections, and can contribute to development of neoplasia. Determination of cervico-vaginal bacteria that mediate immunomodulatory mechanisms will help to study in more detail the properties of antimicrobial molecules (B-defensin, lipocalin, elafin, secretory leukocyte protease inhibitor, IgA, IgG), which are directly involved in maintaining the balance of the vaginal ecosystem, and establish preventive and therapeutic strategies for prevention and elimination of a number of sexually transmitted infections.