From 2013 to 2017, drug overdose deaths in the United States increased, with two-thirds involving opioids. Synthetic opioids, including illicitly manufactured fentanyl, were a major contributor to the rise in overdose deaths. In 2017, 67.8% of drug overdose deaths involved opioids, with significant increases in synthetic opioid-related deaths. The rate of synthetic opioid-involved overdose deaths increased by 45.2% from 2016 to 2017. The epidemic has affected all age groups, racial/ethnic groups, and urbanization levels, with the largest relative increase in deaths among non-Hispanic blacks. Prescription opioid-involved deaths remained stable, while heroin-involved deaths showed some decline. However, synthetic opioid-involved deaths continued to rise, driven largely by fentanyl and its analogs. The epidemic has worsened, with increasing complexity due to the co-involvement of prescription and illicit drugs. The CDC is working to improve surveillance and data collection to inform prevention and response strategies. Although some preliminary data from 2018 suggest potential improvements, confirmation is needed. Continued efforts are essential to address the opioid epidemic, including improved toxicologic testing, naloxone availability, and medication-assisted treatment. Public health partnerships and evidence-based interventions are crucial to reducing overdose deaths.From 2013 to 2017, drug overdose deaths in the United States increased, with two-thirds involving opioids. Synthetic opioids, including illicitly manufactured fentanyl, were a major contributor to the rise in overdose deaths. In 2017, 67.8% of drug overdose deaths involved opioids, with significant increases in synthetic opioid-related deaths. The rate of synthetic opioid-involved overdose deaths increased by 45.2% from 2016 to 2017. The epidemic has affected all age groups, racial/ethnic groups, and urbanization levels, with the largest relative increase in deaths among non-Hispanic blacks. Prescription opioid-involved deaths remained stable, while heroin-involved deaths showed some decline. However, synthetic opioid-involved deaths continued to rise, driven largely by fentanyl and its analogs. The epidemic has worsened, with increasing complexity due to the co-involvement of prescription and illicit drugs. The CDC is working to improve surveillance and data collection to inform prevention and response strategies. Although some preliminary data from 2018 suggest potential improvements, confirmation is needed. Continued efforts are essential to address the opioid epidemic, including improved toxicologic testing, naloxone availability, and medication-assisted treatment. Public health partnerships and evidence-based interventions are crucial to reducing overdose deaths.