Potentially inappropriate medications (PIMs) continue to be prescribed and used as first-line treatment for the most vulnerable of older adults, despite evidence of poor outcomes from the use of PIMs in older adults. PIMs now form an integral part of policy and practice and are incorporated into several quality measures. The specific aim of this project was to update the previous Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse drug events (ADEs) in older adults. This was accomplished through the support of The American Geriatrics Society (AGS) and the work of an interdisciplinary panel of 11 experts in geriatric care and pharmacotherapy who applied a modified Delphi method to the systematic review and grading to reach consensus on the updated 2012 AGS Beers Criteria. Fifty-three medications or medication classes encompass the final updated Criteria, which are divided into three categories: potentially inappropriate medications and classes to avoid in older adults, potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate, and finally medications to be used with caution in older adults. This update has much strength, including the use of an evidence-based approach using the Institute of Medicine standards and the development of a partnership to regularly update the Criteria. Thoughtful application of the Criteria will allow for (a) closer monitoring of drug use, (b) application of real-time e-prescribing and interventions to decrease ADEs in older adults, and (c) better patient outcomes.