Gastroesophageal reflux disease (GERD) is associated with ear, nose, and throat (ENT) signs and symptoms. Previously, experiments in animal larynx suggested that acid in combination with pepsin resulted in more laryngeal injury than acid alone. Recently, similar experiments expanded on the above observation, finding no laryngeal inflammation with bile acid, trypsin, or combination of bile constituents in alkaline pH values. Combined, experimental evidence highlights the importance of acidic refluxates that contain pepsin and/or bile acids; however, many patients with laryngeal signs suggestive of GERD do not respond to aggressive acid suppression. This has resulted in controversy about the exact nature of relationship between GERD and ENT signs and symptoms. Because the diagnosis is initially suspected after a laryngoscopic examination by the ENT physicians, the suboptimal clinical response may be caused by the poor specificity of this exam in identifying GERD as the cause of patients' laryngeal symptoms. Hence, a multidisciplinary approach is often required in the optimum treatment of these patients.