The proportion of US overdose deaths involving both fentanyl and stimulants has increased more than 50-fold since 2010. By 2021, stimulants (such as cocaine and methamphetamine) had become the most common drug class found in fentanyl-involved overdoses in every US state. This rise in fentanyl/stimulant fatalities constitutes the ‘fourth wave’ in the US’s long-running opioid overdose crisis.