Gastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated. While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.