This article explores the conditions under which local and regional governments will establish and sustain cross-border co-operation in the fields of police, fire fighting and emergency health services. It argues that understanding this type of cross-border co-operation requires a focus on the way in which professionals define and apply their professional standards in cross-border contexts. Moreover, it requires a focus on individual organizations and professionals working in them, rather than ‘government’ or ‘the state’ as a whole, since cross-border co-operation in these areas typically develops as a result of disparate and unconnected initiatives taken by governmental actors in a given border region. Based on four studies of cross-border co-operation in Dutch border regions, we argue that differences in legal, organizational and cultural backgrounds between the participating countries can be and are overcome by street-level professionals and their organizations, who act as ‘regionauts’ in exploring opportunities for cross-border co-operation. In this type of ‘bottom-up’ cross-border co-operation, motivation among participants is the key to establishing co-operation, and solutions to differences between work routines will be developed along the way. As a result, the establishment of cross-border co-operation often is an experimental, pragmatic enterprise, which is greatly affected by local intra- and inter-organizational dynamics. This opens the potential for pragmatic, flexible and creative solutions. Yet, at the same time it also runs the risk of producing unaccountable cross-border arrangements that are insufficiently embedded in legal and professional safeguards against error and abuse.