Temporomandibular disorders (TMD) comprise the most common cause of chronic facial pain conditions, and they are often associated with somatic and psychological complaints including fatigue, sleep disturbances, anxiety, and depression. For many health professionals, the subjectivity of pain experience is frequently neglected even when the clinic does not find any plausible biologic explanation for the pain. This strictly biomedical vision of pain cannot be justified scientifically. The purpose of this study is to demonstrate, by original articles from the literature and recent studies conducted in our own laboratory, the biological processes by which psychological stress can be translated into the sensation of pain and contribute to the development of TMD. The role of the hypothalamic–pituitary–adrenal axis, the serotoninergic and opioid systems in the pathogenesis of facial pain is exposed, including possible future therapeutic approaches. It is hoped that knowledge from apparently disparate fields of dentistry, integrated into a multidisciplinary clinical approach to TMD, will improve diagnosis and treatment for this condition through a clinical practice supported by scientific knowledge.