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Reflux esophagitis, functional and non-functional. The pathogenesis of gastroesophageal reflux disease has been explained by acid-peptic model. However, related with the progress of the diagnostic modalities, another phenotypical group of patients were defined and called "functional disorders of the esophagus". These patients are important because diagnosis is particularly difficult, co-morbid disorders especially psychiatric diseases are common, proton pump inhibitor response is low, and surgical results are very poor. Simpler and translational science studies are required in functional groups in order to differentiate from acid-peptic disorders. New and more accurate diagnostic modalities as well as therapeutic approaches are strongly needed in this particularly new and exciting era, especially in the effect of neuromodulators. Current diagnostic modalities should also be evaluated and in fact, normal values should be established. New medications, especially acting at the level of esophageal epithelium and intercellular spaces, might shift the paradigm.