To understand the phenomenon of sleep-related gastroesophageal reflux, it is necessary to understand how sleep alters basic physiologic mechanisms. Several mechanisms are depressed during sleep, which may lead to prolonged acid contact times. These mechanisms include the warning signal of heartburn, the frequency of swallowing, and the suppression of salivary secretion. Several investigations have shown that esophageal acid clearance is significantly prolonged during sleep, compared with the waking state; this is true even when sleeping subjects are compared with awake subjects in the supine position. Studies have also demonstrated an enhanced risk of pulmonary aspiration of gastric contents associated with depressed consciousness, likely related to the depression of upper airway protective mechanisms such as cough and swallowing. Available data also support the theory that certain endogenous response mechanisms involving the central nervous system that protect against the potentially damaging consequences of prolonged acid mucosal contact are invoked during sleep.