Chronic orofacial pain is a prevalent problem that encompasses numerous disorders with diverse causes and presenting symptoms. Compared with men, women of reproductive age seek treatment for orofacial pain conditions, as well as other chronic pain disorders more frequently. Important issues have been raised regarding gender and sex differences in genetic, neurophysiologic, and psychosocial aspects of pain sensitivity and analgesia. Efforts to improve our understanding of qualitative sex differences in pain modulation signify a promising step toward developing more tailored approaches to pain management.