In the last few decades, there was a markedly rise in the prescriptions of gastric acid-suppressing agents, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), for the treatment of gastro-oesophageal reflux disease in both adults and children. Along with this, there have been increasing safety concerns about the use of these agents, particularly in young children and infants. Adult studies reported that long-term use of gastric acid suppressants was associated with increased risks of respiratory and gastrointestinal tract infections, vitamin B12 deficiency, hypomagnesaemia, bone fractures and rebound hyperacidity after discontinuation. The proposed pathogenic mechanisms of acid suppressant-associated infections were related to inhibition of gastric acid secretion, alterations of the gut microbiome and immunity. A recent large cohort study in children showed that the use of acid suppressants was associated with a doubled risk of community-associated pneumonia. Although there are limited data in the paediatric population, current evidence suggests that the acid suppressants are not free of adverse drug reactions. Advocating a rationale individualised approach and appropriate use of these drugs would minimise any serious adverse consequences.