This report presents the activities implemented by the EMCDDA and Europol in 2010 in support of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances (hereinafter referred to as the Decision) (1). During 2010, 41 new psychoactive substances were officially notified for the first time in the European Union through the information exchange mechanism, the Early-Warning System (EWS), which was set up by the Decision. The number of new compounds reported in 2010 was higher than ever; the list of newly notified substances was rather diverse and included a plant-based substance, synthetic derivatives of well-established drugs, as well as substances that can be described as ‘designer medicines’. Under the so called ‘Spice’ phenomenon, 11 new synthetic cannabinoids were reported, bringing the total number of synthetic cannabinoids monitored by the EWS to 21. The report also highlights the emergence of 15 new synthetic cathinone derivatives and notes the appearance for the first time of derivatives of phencyclidine (PCP) and ketamine.