A recent study published in Addiction examined polysubstance overdose deaths in the United States during the transition to the fourth wave of the drug overdose crisis. The researchers analyzed national death records from 2010 to 2021 and found an over 50 fold increase in overdose deaths involving both fentanyl and stimulants, with the most substantial rise occurring in 2015. Initially, fentanyl was commonly found alongside prescription opioids, benzodiazepines, and alcohol, but the co-involved substances shifted over time. Heroin-fentanyl co-involvement was prevalent in the Northeast in the mid-2010s, while cocaine-fentanyl co-involvement became widespread by 2021. Methamphetamine-fentanyl co-involvement predominated in the West and in most states in the South and Midwest by 2021. The study highlights the complex dynamics of the overdose crisis, with stimulants becoming the most common drug class involved in fentanyl-related overdoses in every state by 2021, presenting new and evolving public health challenges.