Potent synthetic opioids, illegally produced, are starting to emerge in Europe. Considering the damaging harms caused by the opioid crisis in North America, which has led to a substantial surge in overdose deaths, it is crucial that European leaders understand the challenges associated with synthetic opioids. In this Perspective, we present and discuss the current situation in Europe concerning synthetic opioids, and draw on earlier and ongoing crises involving this group of substances to reflect on likely challenges ahead and ways to improve preparedness.