Physiologic GER may be a maturational phenomenon, because infants outgrow this over time. Many aspects of GERD in neonates and young infants remain incompletely understood, however, particularly the pathophysiology and long-term problems in high-risk neonates. Diagnostic and therapeutic availability is vital in infants with GER and airway compromise, apnea events, or chronic lung disease. Although most infants improve with conservative therapy, there is a dire lack of ideal pharmacologic agents that work on all the mechanisms of GER with the least consequences. Studies that permit diagnosis not only of the disease but also of the causal mechanism, better feeding strategies, and prevention of morbidity from GERD will be beneficial.