The U.S. opioid epidemic continues to worsen, with drug overdose deaths nearly tripling from 1999 to 2014. In 2014, 60.9% of 47,055 drug overdose deaths involved opioids. The CDC examined drug overdose death rates from 2010 to 2015 and opioid overdose death rates from 2014 to 2015, stratified by demographics, region, and specific opioid types. From 2015, drug overdoses resulted in 52,404 deaths, including 63.1% involving opioids. While methadone death rates declined by 9.1%, deaths involving heroin and synthetic opioids (likely driven by illicitly manufactured fentanyl) increased sharply. A multifaceted, collaborative approach is needed, including implementing CDC guidelines for opioid prescribing, improving prescription drug monitoring, expanding naloxone distribution, enhancing treatment capacity, and supporting law enforcement strategies to reduce the illicit opioid supply.The U.S. opioid epidemic continues to worsen, with drug overdose deaths nearly tripling from 1999 to 2014. In 2014, 60.9% of 47,055 drug overdose deaths involved opioids. The CDC examined drug overdose death rates from 2010 to 2015 and opioid overdose death rates from 2014 to 2015, stratified by demographics, region, and specific opioid types. From 2015, drug overdoses resulted in 52,404 deaths, including 63.1% involving opioids. While methadone death rates declined by 9.1%, deaths involving heroin and synthetic opioids (likely driven by illicitly manufactured fentanyl) increased sharply. A multifaceted, collaborative approach is needed, including implementing CDC guidelines for opioid prescribing, improving prescription drug monitoring, expanding naloxone distribution, enhancing treatment capacity, and supporting law enforcement strategies to reduce the illicit opioid supply.