The available evidence from randomized clinical trials or meta-analyses on the therapeutic efficacy of psychotropic drugs and, specifically, of antidepressants, in functional gastrointestinal disorders (FGD), are recent and still fairly limited. The use of these drugs is based on the frequent association of anxiety and depression or neurosis in patients with FGD who seek medical care and on the demonstrated efficacy of these drugs in relieving chronic pain, whatever its origin or localization, for more than 30 years. Antidepressants, even in doses under the antidepressant range, are antinociceptive due to their central and peripheral neuromodulatory effect, which is completely independent of anticholinergic, spasmolytic or antidepressant effects. This has been demonstrated in both animals and humans and, as occurs with another antinociceptive drugs such as clonidine, is mediated by alpha-adrenoreceptors. The choice of antidepressant depends both on the evidence of its analgesic activity (in general greater with tricyclic antidepressants than with the more modern selective serotonin reuptake inhibitors) and on the presence of drug-related adverse effects, which include not only anticholinergic adverse effects but also the possibility of hypotension or cardiotoxicity, which should be avoided. The main selection criteria are demonstrated efficacy and safety. Antidepressants have been shown to be effective in the specific field of non-coronary chest pain probably originating in the esophagus unrelated to gastroesophageal reflux disease, especially mianserin and trazodone, and the effect is maintained in the long term in nearly three-quarters of treated patients. Tricyclic antidepressants have also been shown to be effective in the treatment of abdominal pain in patients with irritable bowel syndrome, with an OR of 4.2 and an NNT of 3.2 in comparison with placebo. In contrast, there is insufficient evidence to recommend the use of antidepressants in functional dyspepsia.