Unique compositional and functional features of the cervicovaginal microbiota have been associated with protection against and risk for sexually transmitted infections (STI). In men, our knowledge of the interaction between the penile microbiota and STI is less developed. The current state of our understanding of these microbiota and their role in select STIs is briefly reviewed, along with strategies that leverage existing findings to manipulate genital microbiota and optimize protection against STIs. Finally, we focus on major research gaps and present a framework for future studies.