Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogues in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are ‘low use but high risk/harm’ substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localised. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users.