With the emergence of more and more synthetic substances since the 1960s, and broader use occurring from the 1980s onwards, there has been an increasing commodification of the market in novel psychoactive substances (NPS). The European Union (EU) took an active stance as regards the regulation of these new substances. Finding itself at the crossroads of public health policy, criminal law and judicial cooperation, the NPS market flouts Member States’ borders and offers a nice field of experimentation to develop the European integrationist project. This contribution presents the development and current state of the cooperation as regards NPS legislation within the EU. The first part discusses the background and history of the first EU legislative efforts to deal with NPS. The second part reviews the current European governance framework that establishes a supranational regulatory focus for this emergent public health threat. The third part evaluates the legal impact of this European supranational response. Finally, the relevance of the EU strategy and its future are briefly discussed in the conclusion.