OBJECTIVE: The vaginal microbiome is a dynamic environment, depending on the results of a complex interplay between microbiota and the host. In physiological conditions, Lactobacillus species are the most represented, regulating glycogen metabolism in order to maintain normal pH. Vaginal flora has been divided into five subtypes. Pattern recognition receptors are present on both squamous epithelial cells lining the vagina and columnar cells lining the upper female genital tract. They respond directly to bacterial product expressed by vaginal microbiome. The vagina contains different immune related cells and receptors which can recognize and react with the microbial environment. Altered microbiota and altered interplay between microbiota and immune system underlie several gynecologic diseases. MATERIALS AND METHODS: In this review, literature data related to vaginal microbiota, vaginal inflammation, immune system and menopause, preterm labor and miscarriage, were summarized. Relevant publications were retrieved from: PubMed, Medline, Scopus and Web of Science. RESULTS: The vaginal microbiome and the relationship with immune system has been analyzed in different gynecologic conditions. Menopause is associated to estrogen loss which causes vaginal atrophy, reduced abundance of Lactobacilli and increased amount of other bacterial species. Estrogens influence vaginal immunity through known and unknown mechanisms. In bacterial vaginosis (BV), due to many bacterial species, there has been found an inhibition of the chemotaxis and cytokine secretion. A decreased concentration of Lactobacilli seems to be playing a role in preterm labor as well as the increased levels of pro-inflammatory cytokines. Finally, the disequilibrium in the Th1/Th2 immune adaptive response, with a shift from Th2 to Th1, appears to be playing a role in miscarriage. CONCLUSIONS: The interplay between microbiota and the host closely involves the immune system. In particular, the vaginal microbiota is classically characterized by Lactobacilli even if vaginal microbiome of asymptomatic woman of reproductive age includes multiple aerobic and facultative or obligate anaerobic species. The role of microbiota and immune system in determining gynecological and obstetric events has been studied throughout recent years reaching new advancements. Therefore, additional studies are needed to better comprehend the complexity of the issue.