It is well-known that development is uneven across regions. The current academic and political consensus calls for policy interventions targeted towards a more balanced, inclusive and regionally cohesive growth. Yet, despite decades of sizeable policy efforts, there is no clear evidence of economic and social convergence across regions within countries. Entrepreneurship and innovation are proven to be strong drivers of regional economic development, and therefore they offer a source of potential solutions to the challenges imposed by an adverse international context. However, both entrepreneurial and innovative activity are themselves highly unevenly distributed in space, which might in itself be a main cause of the persistent regional inequalities in both developed and developing countries. A deeper understanding of the drivers and the implications of sub-national disparities in entrepreneurship and innovation is therefore a priority for implementing policies aimed at unlocking the potential of all regions in order to maximize their contribution to national growth and prosperity. In this introductory chapter, we create a background and a foundation for the rest of the chapters in this edited volume. © Iréne Bernhard, Urban Gråsjö and Charlie Karlsson 2021.