The current review summarizes and attempts to place in proper perspective the past year's literature regarding purported adverse effects of proton pump inhibitors (PPIs).Although generally considered safe, physicians are inundated with retrospective database-driven epidemiologic studies, and meta-analyses on the same studies, claiming a panoply of serious adverse effects associated with long-term use of PPIs. The quality of the evidence underlying most of these associations is very low and cannot ascribe cause and effect. Nonetheless, these reports have stoked fears, in both prescribers and patients. As a result, patients are being harmed. Physicians are not prescribing PPIs when medically indicated and patients are stopping PPIs without consulting their caregivers. It is reassuring that a cross-sectional analysis of data from the National Ambulatory Medical Care Survey as well as a double-blinded, placebo-controlled trial report no safety concerns with PPIs, other than a possible small association with enteric infection.Most of the publicized serious putative adverse effects attributed to PPIs have been debunked in more recent and properly designed studies. Nevertheless, PPIs should be prescribed for valid indications and, when prescribed long-term, they should be used at the lowest effective dose and their ongoing need periodically assessed.