Aims: To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interventions in the treatment of chronic temporomandibular disorders (TMD), including rheumatoid arthritis (RA), as well as atypical facial pain (AFP), and burning mouth syndrome (BMS). Methods: Study selection was based on randomized clinical trials (RCTs). Inclusion criteria included studies on adult patients (>= 18 years) with TMD, RA of the temporomandibular joint (TMJ), AFP, or BMS and a pain duration of > 3 months. Data sources included Medline, Cochrane Library, Embase, and PsychLitt. Results: Eleven studies with a total of 368 patients met the inclusion criteria. Four trials were on TMD patients, 2 on AFP, 1 on BMS, 1 on RA of the TMJ, and 3 on mixed groups of patients with TMD and AFP. Of the latter, amitriptyline was effective in 1 study and benzodiazepine in 2 studies; the effect in 1 of the benzodiazepine studies was improved when ibuprofen was also given. One study showed that intra-articular injection with glucocorticoid relieved the pain of RA of the TMJ. In 1 study, a combination of paracetamol, codeine, and doxylamine was effective in reducing TMD pain. No effective pharmacologic treatment was found for BMS. Only minor adverse effects were reported in the studies. Conclusion: The common use of analgesics in TMD, AFP, and BMS is not supported by scientific evidence. More large RCTs are needed to determine which pharmacologic interventions are effective in TMD, AFP, and BMS. Palabras clave: orofacial pain, pharmacologic treatment, randomized clinical trials, systematic review, temporomandibular disorders