INTRODUCTION: Optimal management of provoked vestibulodynia (PVD), thought to be the most common form of chronic dyspareunia, is unclear. AIM: To integrate recent brain data on chronic pain circuitry with stress-induced neuroendocrine mechanisms in the skin and the stress burden (allostatic load) of women with PVD; to also clarify the typical chronicity and negative sexual sequelae associated with PVD; and then review modulation of pain circuitry by cognitive therapy and mindfulness practice and apply to PVD management. Methods.? Review of scientific publications in the areas of sexual medicine, pain, brain imaging, gynecology, stress response, mindfulness, and cognitive behavioral therapy (CBT). MAIN OUTCOME MEASURES: (i) A model of PVD to reflect its etiology, typical chronicity, and the detrimental effects on sexual function; (ii) Interventions of sexual rehabilitation based on principles underlying changes associated with CBT and mindfulness practice. RESULTS: A model emerges which reflects how stress-induced changes of pain amplification (central sensitization), characteristic of chronic pain conditions, may impair sexual response in addition to sexual dysfunction that arises from conscious pain avoidance and/or fear-related inattention to sexual cues. Stress from low self-acceptance may be a major component of the allostatic load present in women with PVD, only to be exacerbated by the sexual dysfunction precipitated by the pain of intercourse. Mindfulness-based CBT appears promising to target both the pain and sexual suffering from PVD. CONCLUSION: New findings on brain activity associated with recurrent clinical pain, functional brain changes associated with CBT and mindfulness, plus new data on stress systems within the skin along with data on increased stress load in women with PVD, support the use of mindfulness-based CBT for the recurrent pain and sexual suffering from PVD.