It is not well understood why some healthy vaginal microbiomes are dominated by Lactobacillus and some are not. This review outlines factors which impact the vaginal microbiome and may explain this phenomenon. Specifically, hygiene practices, diet, sexual partners and practices, gender affirming treatments, stress, and social determinants are discussed. The goal of this review is to discuss key endogenous and exogenous factors that clinical experts and research scientists should consider when evaluating the vaginal microbiome in health and disease.