The vaginal microbiome plays an important role in vaginal health and disease. For example, certain Lactobacillus species dominate in a healthy vagina, while disruption of the microbial status quo is associated with disease. Therapies to manipulate the vaginal microbiome are therefore promising for preserving vaginal health, but no preclinical models have been able to faithfully replicate the vaginal epithelial microenvironment for experimentation, until now. Researchers at the Wyss Institute at Harvard have just developed the Vagina Chip, a 3D in vitro model featuring a functional vaginal epithelium. When assemblages of beneficial vaginal microbes like Lactobacillus crispatus are grown on the chips, the epithelial cells remain healthy. In addition, beneficial D- and L-lactate accumulate, a normal vaginal pH is maintained, and proinflammatory molecules are downregulated. In contrast, when groups of harmful bacteria like Gardnerella vaginalis are grown on the chips, the epithelial cells become damaged and the pH and proinflammatory cytokine levels increase, consistent with the pathological changes in a human vagina with an unhealthy microbiome. Although additional confirmation is needed, the findings demonstrate that the new Vagina Chip is a promising preclinical model that can be used to clarify vaginal epithelium– microbiome interactions and test new therapies.