A three-tiered defense system exists in the esophagus, which serves a dual purpose of both limiting the degree of gastroesophageal reflux and minimizing the risk of acid-induced mucosal injury. The antireflux barrier, composed of both the lower esophageal sphincter and the diaphragmatic pinchcock, is the first line of defense and serves to limit the frequency and volume of refluxed gastric contents. When the antireflux barrier fails, the second line of defense, esophageal clearance, comes into play and serves to limit the duration of contact between gastric contents and the esophageal epithelium. Mechanisms involved in esophageal clearance include gravity and esophageal peristalsis, which remove volume, and secretions from swallowed saliva and esophageal submucosal glands, which neutralize acid. The third line of defense, tissue resistance, is necessary when acid contact time is prolonged such as when esophageal clearance is either ineffective or not operative (e.g., during sleep). Most studies that have examined esophageal clearance mechanisms have focused on the roles of esophageal peristalsis and salivary secretion, but the role of submucosal gland secretions is less well understood. This article reviews the structure and function of esophageal submucosal glands and discusses the potential role of their secretory products in esophageal clearance and tissue resistance.