Reply: We appreciate the comments discussed in the letter by Drs Gunasekaran, Kakodkar, and Berman. Although the authors lay out the case for the differential pharmacokinetics of proton pump inhibitors in infants as a reason for cautious prescribing, we wanted to highlight that the main reason not to prescribe these medications in infants is because they are not efficacious in treating symptoms in otherwise healthy infants. Despite the fact that between 23% and 71% of infants are prescribed either an H2 antagonist or a proton pump inhibitor worldwide, there are multiple studies including placebo-controlled trials showing a lack of benefit of acid suppression in improving symptoms of fussing, crying, arching, apnea, cough, hoarseness, wheezing, or feeding intolerance (1–4). The lack of efficacy may be multifactorial; symptoms may not be reflux related or the reflux is a result of nonacidic gastric contents getting refluxed (ie, formula or breast milk) upon which acid suppression has no effect. So, although consideration of pharmacokinetics and side effects are important when prescribing, the biggest deterrent should be that these medications have consistently been shown not to improve symptoms. There are 2 notable populations in whom acid suppression is warranted, those patients at high risk for esophagitis and those with confirmed histologic esophagitis with eosinophilic infiltrates. Children with esophageal motility disorders such as treated achalasia or esophageal atresia fall into this first category; any reflux that enters the esophagus is poorly cleared because of profound disturbances of peristalsis. Recognizing the impact of dysmotility on poor reflux clearance is critical and, this population, we feel, merits aggressive acid suppression therapy with proton pump inhibitors to prevent long-term reflux complications including erosive esophagitis, metaplasia of esophageal epithelium, and stricturing (5). Apart from patients with dysmotility, a second population meriting therapy includes symptomatic infants with eosinophilic infiltration of the esophagus in whom proton pump inhibitor (PPI) therapy may help to narrow the differential diagnosis including eosinophilic esophagitis, proton pump inhibitor responsive eosinophilic esophagitis, and reflux esophagitis. As with all medications, prescribing needs to be done thoughtfully and the pathophysiology of the signs and symptoms needs to be considered. We whole heartedly agree that there is a limited role for proton pump inhibitors in infants. Those infants with motility disorders and confirmed esophagitis do, however, merit therapy. Again, we assert that once prescribed, the benefit/risk ratio of long-term PPI treatment should be balanced, and the need of prolonged use of PPIs should be reassessed on a regular basis.