In 2009 the European Union (EU) introduced the macro-regional strategy approach as a policy framework allowing countries located in the same region to jointly tackle common challenges. There is no doubt that macro-regional approaches can pave the way towards a more innovative, sustainable and greener Europe. But to make it work, the involved actors need to become determined about funding cross-regional research, development and innovation (RDI) projects. The macro-regional innovation motors need sustainable new power sources. It is time for a wave of new cross-regional funding schemes dedicated to RDI across borders.