Gastroesophageal reflux (GER) is the retrograde movement of gastric (and sometimes duodenal) contents into the esophagus. While the majority of GER is physiologic, for patients, it can be associated with symptoms. While some symptoms are merely bothersome (crying), others can be life threatening (cough, gagging, choking). The main driver of GER in infants is the frequent feedings that produce increased intra-abdominal pressure, which is known to trigger transient relaxations of the lower esophageal sphincter. The recent 2018 clinical practice guidelines reported by the North American and European Societies for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN/ESPGHAN) have recommended non-pharmacologic management initially with subsequent consideration of brief trials with acid suppressants. The main target for these acid suppressants is the gastric parietal cells. Our review of the literature has revealed a paucity of data regarding the use of histamine-2 receptor antagonists and proton pump inhibitors in infants. Despite the absence of well-controlled clinical studies, the prescription rate of these medications has increased internationally. Risks to patients of all ages have become increasingly recognized, with new associations being reported all too often. Here we report our review of all pharmacologic modalities as well as some non-surgical options.