<p>Proton pump inhibitors (PPIs) are amongst the most commonly prescribed medications worldwide. Clinical practice guidelines identify clear indications for short-term and long-term use; however, many older adults are prescribed potentially unnecessary PPIs. Multiple concerns exist with unnecessary PPI therapy, including the potential long-term risk of adverse effects. An association between PPI use and fractures, dementia, and respiratory and gastrointestinal infections has been suggested in observational data; however, there is a paucity of high-quality data supporting a causative relationship. Despite this, PPIs remain a target for medication optimization in older adults because of the high rate of unnecessary use, cost, and contribution to pill burden and polypharmacy. A multidimensional approach is required to reduce unnecessary PPI’s, including the alignment of initial prescribing with evidence-based indications, reassessment of existing prescriptions, enhancement of knowledge and resources for patients and prescribers, and support for deprescribing. To increase deprescribing success, barriers to PPI deprescribing must be addressed, including the fear of symptom recurrence, insufficient time and education, and lack of concern regarding long-term use. Deprescribing strategies, such as tapering, can aid in success, as can the utilization of nonpharmacological and lower risk options for managing symptoms of gastric-acid-related disorders.</p>