Advances in esophageal sensory stimulation have established that both typical and atypical symptoms may not only arise from acid reflux, but also from reflux events with less acidic pH (pH 4-7). Literature review shows that in GERD patients with persisting symptoms in spite of PPI therapy, ongoing weakly acidic reflux can be considered as an important underlying factor. The basis for symptom generation during weakly-acidic reflux events remains to be determined, but acid sensitivity in the pH range 4-7, mechanical distention (enhanced by air in the refluxate), sensitivity to other chemical factors (e.g. bile salts) and esophageal hypersensitivity to physiological levels of reflux have all been proposed.