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To review published literature for the highest level of evidence on the efficacy of treatment for patients with medically unexplained symptoms.A comprehensive literature search was carried out in Cochrane library, Medline (1971–2007), PsychINFO (1974–2006), and EMBASE (1980–2007) to identify pharmacological, nonpharmacological, psychological, and other interventions, using the search terms “medically unexplained symptoms,” “somatisation,” “somatization,” “somatoform disorders,” “psychological therapies,” “cognitive behavior therapy,” “pharmacological therapies,” “management,” “therapy,” “drug therapy,” and “anti-depressants” with Boolean operators AND and OR on the entire text. Searches were confined to literature in English.Studies were carried out in primary, secondary, and tertiary care settings. The therapists ranged from medical specialists, psychiatrists, and psychologists to primary care physicians. Three types of interventions (antidepressant medication, cognitive behavioral therapy (CBT), and other nonspecific interventions) were supported by evidence on the efficacy of treatment for patients with medically unexplained symptoms. There is more level I evidence for CBT compared with the amount for other approaches. There was only one study reported from the developing world.CBT is efficacious for either symptom syndromes or for the broader category of medically unexplained symptoms, reducing physical symptoms, psychological distress, and disability. A relatively small number of studies were carried out in primary care, but the trend has been changing over the last decade. No studies have compared pharmacological and psychological treatments. Most trials assessed only short-term outcomes. Use of divergent selection procedures, interventions, outcome measures, and instruments, and other methodological differences observed in these studies hamper the ability to compare treatment effects across studies.