Gastroesophageal reflux is a normal physiologic occurrence that is common throughout infancy and usually resolves on its own. Infrequently, reflux causes complications and turns into gastroesophageal reflux disease (GERD), which may warrant intervention. Available interventions vary in invasiveness and supporting data may be lacking for efficacy and safety. Nonpharmacologic interventions are first-line therapy for GERD in infants, whereas pharmacologic and surgical approaches are controversial. Efficacy data are limited for pharmacologic strategies for infantile GERD and safety data have demonstrated serious risks, especially in younger infants. Utilization of these medications should be approached cautiously in this population, if appropriate diagnostic techniques determine acid suppression could be beneficial. A robust monitoring plan with frequent reassessment of need for therapy may optimize benefit and minimize risk.