More than one million women are infected with HIV annually. However, the biological mechanisms associated with transmission in women are not well understood. One factor that has consistently been associated with increased acquisition of HIV in women is imbalanced vaginal bacteria, i.e. vaginal microbiome dysbiosis. Lack of healthy Lactobacillus bacteria, but increased anaerobic bacteria and higher diversity of the microbiome in the female reproductive tract has been associated with clinical vaginosis, inflammation, and increased HIV infection. We recently demonstrated that dysbiotic vaginal bacteria can also alter the efficacy of topical pre-exposure prophylactic (PrEP) strategies. We found the mechanism by which dysbiotic bacteria decrease efficacy of topical antiretroviral-based PrEP is by direct metabolism of the drugs by bacteria. Here we will summarize what is currently known about vaginal microbial dysbiosis and HIV infection, and the potential mechanisms of how vaginal bacteria may influence HIV transmission in women.