This chapter addresses the challenges posed in Europe to second-rank cit-ies by the university institutions located within their boundaries. The main thesis is that universities, while also having a key role in European nation-capital cities, like Rome or Berlin, or in world-class metropolises, like Paris and London, exert their driving force best in small and medium-sized cities. Here, universities can be new engines of cultural and economic landscapes. These engines are so powerful that the growth of many European cities and surrounding regions depend on how successful they are in attracting the key factors of university life: public investments in research and education, the best faculty staff, students, private entrepreneurs, and philanthropic actors. In addition, university cities may take advantage of a free and constant flow of communication activities directed both to selected audiences of investors and to the general public, generated by locally-based universities.