The purpose of this article is to assist emergency physicians in selecting safe and effective drug therapy for seniors. Because safer alternatives exist, medications on the Beers list of potentially inappropriate medications should generally be avoided. We also review risks associated with several classes of medications: nonsteroidal anti-inflammatory drugs, benzodiazepines, and anticholinergic medications. They are associated with adverse outcomes when taken by older adults and should be used with caution. We also address the use of opioid medications in seniors. Although they are not without risk, opioids are generally safe with slow titration, precautions, and a bowel regimen to prevent constipation. Prescribers should also consider the need for estimating creatinine clearance when prescribing medications that require dosage adjustment in the setting of renal insufficiency. Two areas in need of research are identifying the proper dosing and safety of medications in seniors and prescribing with electronic decision support to assist in prescribing decisions.