In this paper, we review and comment upon the development of the literature on diversity, innovation, and entrepreneurship. In an overview of previous studies and various strands of literatures, we outline and argue that to better understand the intricate dynamic relationships between diversity, innovation, entrepreneurship, and regional development there is a strong need to further develop “the economics of spatial diversity.” We further argue that this development may benefit from combining various literatures based upon sound economic micro-foundations, to develop a more absolute understanding of diversity and fulfill the need of more clear mechanisms for future empirical testing. Obviously, this is important both from a research point of view and in order to provide policymakers with a powerful set of analytical tools. We call for more analytical work and more high-quality empirical studies. With a set of papers, we believe this special issue to provide a contribution in this direction.