Emergency department (ED) visits for opioid* overdoses rose 30% in all parts of the US from July 2016 through September 2017. People who have had an overdose are more likely to have another, so being seen in the ED is an opportunity for action. Repeat overdoses may be prevented with medication-assisted treatment (MAT) for opioid use disorder (OUD), which is defined as a problematic pattern of opioid use. EDs can provide naloxone, link patients to treatment and referral services, and provide health departments with critical data on overdoses. ED data provide an early warning system for health departments to identify increases in opioid overdoses more quickly and coordinate response efforts. This fast-moving epidemic does not stay within state and county lines. Coordinated action between EDs, health departments, mental health and treatment providers, community-based organizations, and law enforcement can prevent opioid overdose and death.