Since the arrival on the scene of Joseph Schumpeter's groundbreaking body of thought, it has been clear that innovation and entrepreneurship are closely interrelated. This interrelation has become the point of departure for a wide range of studies that make the link between innovation, entrepreneurship and economic growth. In particular, in recent years the interaction between innovation, entrepreneurship and regional economic development has become a central theme in many policy circles. Examples such as Cambridge U.K. and Cambridge U.S., and, more emphatically, the phenomenon of Silicon Valley, are the driving forces behind this interest. Today almost every European region is attempting to put together the ingredients necessary for endogenous economic growth, based on the innovative capacity and the entrepreneurial dynamics that can be mobilised in a particular region. The realisation of such endogenous growth does, however, necessitate a deeper insight into the parameters and the dynamics upon which it is based. That is the first aim of this contribution. On the basis of both a study of the literature and empirical data, the authors offer an overview of and an insight into the manner in which knowledge-driven entrepreneurship can flourish. The results of this synthesis point to the necessity for a complex and guided interaction between knowledge creating institutions (like universities and research centres), established businesses and new start-ups, with sufficient attention paid to the network of professional enterprises and infrastructure which frames such interaction. Drawing on examples from the United States, and Europe, this synthesis will be further substantiated, leading to the conclusion that knowledge driven entrepreneurship, i.e. the genesis and development of high tech entrepreneurial activities, can not be confined to individual entrepreneurial activity. Entrepreneurship finds it origins and growth in a multitude of interactions, which unfold amongst a variety of actors. As such our contribution implies a direct plea for broadening the way entrepreneurship is being studied and looked upon. Secondly, we want to illustrate how one can foster such dynamics by installing supportive arrangements that address critical ingredients and facilitate relevant interactions. This will be done by examining the experience build up over the last decades in Leuven (Belgium) in more depth.