Distressful symptoms associated with gastroesophageal reflux constitute a clinical description of gastroesophageal reflux disease, a pathologic condition commonly treated with proton pump inhibitors (PPIs). Despite their pervasive use in neonates and infants, PPIs have not been approved for gastroesophageal reflux disease treatment in this population. This creates a therapeutic conundrum: namely, whether to institute PPI treatment based on knowledge and experience or to withhold it consequent to absence of labeling for young infants.