The pathological underpinnings of localized provoked vulvodynia (LPV), the most prevalent cause of vulvar pain that is frequently comorbid with other variants of chronic pelvic pain, have evaded clinicians and scientists for decades. This commentary describes the background and implications of the findings presented by Foster et al. [6] in this issue. An emphasis is on reasons why the vulvar vestibule—an embryologically distinct band of tissue demarcating the internal female reproductive tract and external vulva—should exhibit a propensity for fibroblast-mediated proinflammatory responses to commonly encountered yeast in healthy women, as well as women with LPV. Foster and colleagues’ findings have the potential to advance the clinical assessment of women with LPV, facilitate the identification of mechanistically distinct comorbid pelvic pain conditions, and guide future animal model development to optimize their clinical relevance.