In this paper, we give a general introduction to the notion of entrepreneurship and how it has many complex meanings. Entrepreneurs in new firms but also in incumbent firms have a key role in local, regional and national economic development by taking risks to get things done by developing new combinations of ideas and/or doing things differently. In view of this, two of the main questions that are dealt with are: (1) which features make structural differences in institutions and innovation networks remain invariant between decades, and (2) how knowledge about such features can be employed in policy at the national and the regional level. The research questions highlighted in this special issue relate to many pertinent national and regional policy issues. The most apparent concerns conditions conducive for entrepreneurship in the form of new firms and firm growth. In this paper, we also introduce the different contributors to this special issue.