Purpose: The purpose of this paper is to introduce the case of the cross-border RCE Rhine-Meuse established as the first Regional Centre of Expertise (RCE) on Education for Sustainable Development in Europe. RCE Rhine-Meuse is an initiative of two institutions of higher education in the South of The Netherlands, but reaching out to the German and Belgian border regions. Design/methodology/approach: The case of the RCE Rhine-Meuse is used to give a comprehensive description of the building of a multi-national and multi-stakeholder collaboration network aiming at knowledge dissemination on education for sustainable development. The regional approach is complementary to the global approach behind the RCE network. Findings: The development of the RCE Rhine-Meuse over the last two years, shows the development of a functional RCE as described by United Nations University. A regional network for collaboration in the field of learning for sustainable development is created. The governance of the RCE is stable and the activities create an added value to the development of the region. Practical implications: The case of the RCE Rhine-Meuse does not provide a blue-print for setting up an RCE like network. What the case of the RCE Rhine-Meuse does show, is the influence of the regional context on the development of the RCE. In addition, the RCE Rhine-Meuse does provide general notions that can be of use for other regions that want to establish an RCE. Originality/value: The case of the building of the oldest RCE in Europe over the period 2004-2008 provides the first comprehensive overview of the creation of a new mechanism that is focussing on knowledge transfer to further regional sustainable development.