Drug overdose fatalities surged during the COVID-19 pandemic in New York State, with opioid-related overdose deaths increasing by 68% to nearly 5,000 individuals from 2019 to 2021. The surge is largely due to a sharp increase in deaths from opioids related to illicit fentanyl and similar synthetic opioids. This report outlines long-term trends and recent developments in the battle to save lives from being lost prematurely to substance use disorder.