The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host-vaginal microbiota interactions in bacterial vaginosis pathogenesis. Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host-immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes. Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.