© 2020 Lippincott Williams & Wilkins. Despite the availability of a number of oral and intravaginal antibiotic medications for the treatment of bacterial vaginosis (BV), management of this condition remains challenging. Recurrent BV occurs in >50% of patients receiving guideline-recommended treatments. This may be due to persistence or resurgence of the BV biofilm after treatment cessation, failure to reestablish an optimal vaginal microbiome after treatment, reinfection from an untreated sexual partner, or a combination of these factors. Nonadherence to multidose BV therapies may potentially contribute to recurrent BV, although there are no published data that directly assess the role of nonadherence to poor treatment outcomes and recurrent BV. There is a need for studies of BV treatment adherence in real-world settings as well as studies to explore the relationship between treatment adherence and recurrence. This review explores challenges associated with diagnosing and treating BV, current multidose antibiotic treatment options, newer single-dose treatment options, and ways to potentially maximize treatment success for this common vaginal infection.