Abstract The use of new psychoactive substances (NPS) became an emerging issue in prisons in a number of European countries in 2014-2015. Synthetic cannabinoids were the new psychoactive substances most often reported, followed by synthetic cathinones, synthetic opioids and new benzodiazepines. Quantitative qualitative data on prison and drugs provided by 27 European Member States, Norway and Turkey to the EMCDDA (European Monitoring Centre for Drugs and Drug Addiction). An exploratory study conducted in 2017 found signs of NPS use in prison in 22 countries. Based on 2021-2022 data from a few countries, the lifetime prevalence of NPS in prison ranges from <1 to 19%, with large variation by country. Anecdotal information from 2024 referred to the use of new strong synthetic opioids (nitazene) inside prison. A wide range of physical and mental health harms (e.g. psychosis, disorientation, suicidal ideation, aggressiveness to others or self-harm) has been associated with acute intoxication by, and chronic consumption of NPS inside prison. Recent overdoses associated with the use of nitazene were reported in some prisons in Ireland and the UK. Additionally, the use of NPS in prison can have a disturbing impact on prison management, internal violence and bullying. To date, interventions to tackle the problems related to the use of NPS in prison have tended to focus on supply reduction and controls. Health and social interventions have begun to emerge, but they remain limited. Despite signs of increasing challenges posed by the emergence of NPS since several years, prisons remain largely unprepared to monitor and respond to those challenges. A new key task of the revised EMCDDA mandate (EUDA - European Drug Agency from 2nd of July) is to be better prepared to monitor, forecast and respond to new challenges in the drug field. Prisons should be prepared to adequately address the new challenges posed by the NPS to benefit the health and security of people living and working in prison.