Proton pump inhibitors (PPIs; e.g. Prilosec/omeprazole, Prevacid/lansoprazole, and others) are among the most commonly used medications, with prevalence estimates ranging between about five percent and fifteen percent of the adult population. Recently, there have been increasing concerns about the safety of long-term PPI use, leading many patients to abandon their PPIs in favor of H2 receptor antagonists (H2RAs; e.g. Pepcid/famotidine, Zantac/ranitidine, Tagamet/cimetidine) or to stop acid suppression therapy altogether. While the tenet of “first, do no harm” remains paramount in the practice of medicine, it is important to use caution when interpreting reports of risks associated with PPI use.