This introduction to the special issue “The Geography of Innovation and Entrepreneurship” in the Annals of Regional Science surveys a collection of nine papers which consider agglomeration economies and spatial heterogeneity of regions and firms through the lenses of innovation and entrepreneurship. They all make use of extensive and detailed data sources that enable models to provide a richer picture of how firms, industries and regions are affected by innovation and entrepreneurship but also how these entities shape and foster renewal. These factors include spatial concentration, industry composition, labor market characteristics, immigration, firm characteristics, R&D activities and R&D collaboration. The papers add to the understanding of the geography of innovation and entrepreneurship by suggesting alternative ways of identifying spillovers, combing and integrating internal and external knowledge sources, and by estimating the impact on innovation, new firm formation and growth.