In recent years, the notion of ‘excellence’ and its interconnectedness with research, development and innovations has become extremely popular across Europe. At regional and national as well as at the EU level, various initiatives have been taken to strengthen the science base, and to establish centres, or clusters of outstanding achievements. Researchers, universities, and funding agencies will have to work their way towards a culture of creativity, which needs a leap of faith based on the high-trust principles of governance and accountability, and which provides more space for risk-taking and thorough rethinking of common wisdom in order to achieve real breakthroughs at the frontiers of knowledge.