Practitioners and patients alike widely recognize the limitations of current therapeutic approaches to the treatment of bacterial vaginosis (BV). Options remain extremely limited, and our inability to prevent the frequently, often relentless symptomatic recurrences of BV and to reduce serious sequelae such as preterm delivery, remains an acknowledged but unresolved shortcoming. Our incomplete understanding of the pathophysiology of this unique form of vaginal dysbiosis has been a significant impediment to developing optimal treatment and prevention approaches. New drugs have not been forthcoming and are not likely to be available in the immediate future; hence, reliance on the optimal use of available agents has become essential as improvised often unproven regimens are implemented. In this review, we will explore the limitations of currently recommended therapies, with a particular focus on the contribution of reinfection and pathogen persistence to BV recurrence, and the development of interventions that target these mechanisms. Ultimately, to achieve sustained cure and effectiveness against BV-associated sequelae, it is possible that we will need approaches that combine antimicrobials with biofilm-disrupting agents and partner treatments in those at risk of reinfection.