Morbidity and mortality from opioid medications constitutes a patient safety problem. This National Academy of Medicine report explores the role of physicians in preventing and treating opioid misuse. The report highlights the increasing rate of opioid prescriptions in parallel with rising numbers of opioid overdose deaths and recommends adherence to clinical guidelines on opioid use, specifically the 2016 CDC guideline. The authors call for improved access to opioid prescription and dispensing data and more stringent regulation of opioid medications. They provide detailed recommendations for clinicians to prescribe opioids more safely, including the use of prescription drug monitoring programs, coprescription of naloxone, and engaging with community resources to identify and treat opioid use disorder. A recent PSNet perspective discussed opioid overdoses as a patient safety problem.