The purpose of this CDC Health Alert Advisory is to alert public health departments, healthcare professionals, first responders, harm reduction organizations, and medical examiners and coroners to 1.) significant increases in drug overdose deaths across the US, driven mostly by synthetic opioids like illicitly manufactured fentanyl 2.) a concerning acceleration of increase in drug overdose deaths, with largest increase recorded March 2020 to May 2020 3.) the changing geographic distribution of overdose deaths involving sythetic opioids, with the largest percent increase occurring in the states of Western US 4.) significant increase in overdose deaths involving psychostimulants with abuse potential such as methamphetamine; and 5. recommendations for communities when responding to the evolving overdose crisis. Steps for professionals and communities to reduce overdose deaths are included in this advisory.