The vaginal microbiota forms the first line of defense against sexually transmitted infection (STIs). Population-based surveys of the bacteria inhabiting the vagina have shown that several kinds of vaginal microbiota exist, that differs in bacterial composition and abundance. Further, in some women, these communities are dynamic and can change over short period of time, while in other, they are highly stable and do not change. The impact of both composition and dynamic of the vaginal microbiota on the susceptibility to diseases is still poorly understood. The application of modern genomic technologies, ecological principles and in vitro modelling affords a better understanding of the role of vaginal microbiome in health and diseases. Metagenomic sequencing provides a comprehensive view of the genetic make up of the bacterial species comprising the vaginal microbiome, and highlights associations between different genomic species of the same genus, or strains of the same species and their contribution to the protective properties of the vaginal microbiome. For example, the genomic make up of certain vaginal bacteria correlates with their ability to maintain a stable and protective vaginal microbiome. Further, the use of in vitro three-dimensional models of cervical epithelial cell lines is a good surrogate to evaluate the contribution of microbial products to the function of the vaginal microbiome. Using a 3D model of cervical epithelial cells, we have shown that the production of different isomers of lactic acid by Lactobacillus spp. is associated with protection against chlamydial infection in a pH dependent manner. Understanding the vaginal microbiome structure and functions is critical to devise novel and personalised strategies to maximise women’s health.