This review addresses the changes in the physiologic responses to esophageal acid contact that occur during sleep. The importance of these changes is addressed as they pertain to the development of esophagitis and other complications of gastroesophageal reflux. Sleep results in physiologic changes that impair esophageal acid clearance, thereby creating a vulnerability to the complications of reflux. These complications are generally considered secondary to prolonged acid mucosal contact. Sleep-related reflux also disrupts sleep, which may result in clinical complaints of sleep disturbance and significant daytime consequences, such as sleepiness and diminished work performance. The significance of these sleep-related findings is addressed in the context of the diagnosis and treatment of GERD.