Studies in which lower esophageal sphincter and esophageal pH have been monitored simultaneously have challenged the traditional concept that most reflux episodes result from weak steady state lower esophageal sphincter tone. Instead, the majority of reflux episodes have occurred during 5–35-second abrupt periods of complete sphincter relaxation usually against a background of normal sphincter tone. This distinctive pattern of relaxation, which has been named “transient lower esophageal sphincter relaxation,” occurs independently of swallowing. It depends on vagal pathways and the hindbrain for its patterning and control, but many of these aspects are still not well understood. Control of transient lower esophageal sphincter relaxation by drug therapy is an attractive future option for management of supraesophageal complications of reflux disease.