Amidst an ongoing opioid crisis that claimed 47,600 lives in 2017, increasing the availability of the rescue medication naloxone is a high priority. Naloxone reverses an opioid overdose when given intranasally or intramuscularly. But to be effective, naloxone must be available at the time of overdose. Naloxone distribution to laypeople can save a life when first responders are not immediately available, or when people witnessing overdoses are unwilling or unable to call 911. Naloxone is increasingly available through some pharmacies under a standing order; however, even when available, cost and stigma barriers persist. This Issue Brief reviews recent evidence on the outcomes and cost-effectiveness of naloxone distribution strategies in community, pharmacy, and other health care settings