Psychoactive medications have been used to manage chest pain of presumed esophageal origin, especially in syndromes associated with esophageal motor dysfunction. The rationale for their use is based on (a) the high prevalence of psychiatric disorders reported in patient groups with esophageal symptoms and minor motor dysfunction, (b) recognized psychophysiologic effects on esophageal motor activity, (c) the potential benefits that nerve-modulating drugs may have on the pathogenesis of the syndromes (independent of psychiatric factors), and (d) observations from treatment trials for chronic pain--including irritable bowel syndrome, a disorder that shares some clinical features with functional esophageal chest pain. Although psychiatric factors may have interactive effects on the presentation and course of reflux disease, the use of psychoactive drugs in reflux disease has not been tested. The effects of psychoactive drugs have been systematically explored and documented in only one study. At present, the mechanisms of esophageal symptom reduction resulting from psychopharmacologic treatments are not clear, but reduced sensitivity to visceral stimuli remains one possibility.