Despite consensus recommendations from the American College of Emergency Physicians (ACEP), the Centers for Disease Control and Prevention, and the surgeon general to dispense naloxone to discharged ED patients at risk for opioid overdose, there remain numerous logistic, financial, and administrative barriers to implementing “take-home naloxone” programs at individual hospitals. This article describes the recent collective experience of 7 Chicago-area hospitals in implementing take-home naloxone programs. We highlight key barriers, such as hesitancy from hospital administrators, lack of familiarity with relevant rules and regulations in regard to medication dispensing, and inability to secure a supply of naloxone for dispensing. We also highlight common facilitators of success, such as early identification of a “C-suite” champion and the formation of a multidisciplinary team of program leaders. Finally, we provide recommendations that will assist emergency departments planning to implement their own take-home naloxone programs and will inform policymakers of specific needs that may facilitate dissemination of naloxone to the public.