AIMS: To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interven-tions 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 (> or = 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 Li-brary, Embase, and Psych Litt. 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 glucocorti-coid 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 sup-ported by scientific evidence. More large RCTs are needed to deter-mine which pharmacologic interventions are effective in TMD, AFP, and BMS.