Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide, and their intake increases with age. Despite a relatively safe profile, a range of studies have reported associations between use of PPIs and various adverse events. The most important adverse events, such as pneumonia, bone fractures, bacterial enteric infections, and diminished vitamin absorption are critically discussed in this review in view of the body of evidence, including underlying biological mechanisms, evidence of causality, and consistency. Most of the reported risks are relatively small and sometimes based on inconsistent evidence. For an individual patient, and particularly the elderly, it is relevant to question the indication of use and balance the benefit and potential harm of PPI therapy. This approach can minimize morbidity and reduce healthcare costs. In this review, the use and safety of PPIs among the elderly is described.