Whereas an impaired antireflux barrier remains a major focus of research on gastroesophageal reflux disease, our current understanding of the nature of this barrier indicates that it is more complex than previously thought. In addition, other factors such as impaired esophageal clearance, gastric hypersecretion, and poor gastric emptying may play a role in reflux disease. Acid suppression continues to have a central role in the treatment of reflux disease. The pharynx and airway are more sensitive to acid than the esophagus and even limited regurgitation of acid into the pharynx may produce extraesophageal manifestations of reflux disease. Consequently, extraesophageal presentations are often more difficult to treat than more typical esophageal manifestations of reflux disease.