This paper is a reflection of the author’s views on recent research developments at the interface of entrepreneurship and regional economic development and growth. The paper begins with an overview of the recent rise of interest in entrepreneurship in general and, in particular, with respect to its influence on regional economic growth and development. Following an introduction the formation and development of high growth firms (HGFs) and their disproportionately large contribution to job creation are examined. Entrepreneurship ecosystems are then examined in an effort to understand the factors that contribute to high levels of HGF production and job growth. This analysis raises a question about the role of culture, governance and institutions in the collage of factors that influence the development of entrepreneurship systems. These factors are then comparatively examined using three case studies for the U.S., Europe and China which raise the question of how to manage the role of government policy to promote entrepreneurship while, at the same time, preserving other seemingly contradictory factors such as risk taking and self-reliance. The last part of the paper focuses on equity considerations that have served as rationales for government intervention in regional and national entrepreneurship systems. Gender, age, migrants, family, technology groups are examined briefly in an effort to provide deeper insight into how public policies in these areas are rationalized. At the end of each major part of the paper relevant research questions are described and discussed. A summary of the paper is presented at the end.