The growing prevalence of gastroesophageal reflux disease (GERD) needs to be carefully managed to relieve the symptoms and prevent complications. Complications of GERD can include erosive esophagitis, Barrett's esophagus and gastrointestinal (GI) bleeding. Proton pump inhibitors (PPIs) are typically first-line treatment for GERD alongside lifestyle changes in view of their effectiveness and cost-effectiveness. However, there are concerns with adherence to dosing regimens and recommended lifestyle changes reducing their effectiveness. There are also concerns about potential complications from chronic high-dose PPIs. These include an increased risk of chronic kidney disease, cardiovascular events and infections. Recommendations to physicians include prescribing or dispensing the lowest dose of PPI for the shortest time, with ongoing patient monitoring. Activities among community pharmacists and others have resulted in increased dispensing of PPIs without a prescription, which can be a challenge. PPIs are among the most prescribed and dispensed medicines in view of their effectiveness in managing GERD. However, there are concerns with the doses prescribed and dispensed as well as adherence to lifestyle advice. These issues and challenges need to be addressed by health authorities to maximize the role and value of PPIs.