No disease has been implicated more frequently as a comorbid cause of upper airway diseases than gastroesophageal reflux disease. Supraesophageal reflux of stomach acid has been suggested to lead to a large number of otolaryngologic conditions, including such disparate morbidities as dysphonia, laryngospasm, vocal cord dysfunction, globus sensation, vocal process granulomas, throat pain, laryngeal cancer, chronic otitis media, rhinitis, asthma, and chronic rhinosinusitis (CRS). Our understanding of the subtleties of upper airway mucosal damage from laryngopharyngeal reflux (LPR) has remained in its infancy throughout the recent past and deserves more attention. Any disease process of the head and neck with a component of inflammation may, in concept, be worsened by the potential damage of acid or nonacid LPR. It is generally unclear from a mechanistic standpoint how simple acid suppression would inhibit the potential upper airway damage of gastric reflux in patients with LPR; most reflux into the pharynx is weakly acidic or nonacidic owing to salivary bicarbonate buffering, and simple acid suppression alone would have minimal effect on overall rates of reflux. Antireflux medications, such as histamine2-receptor blockers and proton pump inhibitors (PPIs) do nothing to stop nonacid reflux, which is likely the majority of reflux that might reach the nasopharynx and contribute to any CRS pathophysiologic processes. Medical treatments for LPR, including trials of empirical PPIs, are expensive, unnecessary, and not without risk. At the same time, the main surgical options to abrogate LPR (such as fundoplication) are often difficult to recommend without concrete evidence of severe gastroesophageal reflux disease owing to the inherent vagueness of the presentation of symptoms of upper airway disease. Endpoints for empirical trials of PPIs are questionable, and the potential for a large amount of placebo effect in the response rate to medication is very real. It is with this background that many well-meaning otolaryngologists often consider trials of PPIs or other antireflux medications for treatment of vague symptoms of upper airway irritation, congestion, and inflammation, including sinus disease.