Forensic DNA profiling and databasing have become increasingly significant resources for criminal investigations in many jurisdictions. More recently, there have been attempts to recruit these technologies into the policing of cross-border organized crime, migration and terrorism. The authors examined the trajectory of one such attempt, the establishment and operationalization of the Prüm Treaty within the European Union. The authors describe the way in which early technological considerations underlying DNA profile exchange, managed within law enforcement bureaucracies, have given way to a concern with broader societal issues and the necessity for a multifaceted scrutiny of this particular technolegal innovation. Central to this issue is the hybrid nature of exchange arrangements created as a result of the European Council Decision on Prüm (2008). The Prüm Treaty departs from the increasingly normalized framework for criminal justice cooperation, and at the same time, does not facilitate DNA exchange within a more traditional multinational instrument. The authors consider the significance and implications of the political decisions behind Prüm, as well as the consequences for the development of transnational DNA exchange in terms of three key issues: technical and scientific challenges (viability); legal challenges (legitimacy); and ethical and socioeconomic challenges (acceptability). Unless the Prüm structure is reformed, an important and promising initiative may remain encumbered with unresolved problems of legitimacy and acceptability. A lack of direct democratic involvement of many member states precluded the creation of consensus on issues such as privacy, data protection and due process issues, upon which legal and political regimes could then act. (Published Abstract)