Opioid pain medications are considered high-risk medications due to the potential for respiratory depression and other adverse effects. Because these medications are frequently used to treat acute pain in the hospital, opioids account for a disproportionate share of preventable adverse drug events. This sentinel event alert, issued by The Joint Commission to highlight particularly important safety issues, calls for hospitals to implement standardized methods to assess and monitor acute pain, ensure education for clinicians on appropriate opioid usage, and use information technology to support safe opioid prescribing. A serious case of opioid overdose is discussed in this AHRQ WebM&M commentary.