This volume provides a collection of theoretical articles and empirical studies on innovation and location by focusing on the institutions and systems that mediate knowledge spillovers. The objective is to provide an international comparison using a variety of approaches. The volume is organized around the three themes. The first focuses on theoretical work that attempts to advance our understanding of knowledge externalities and systems on innovation. The second section provides empirical studies that attempt to measure these impacts. The final section considers future challenges to regional economic development policy in the face of economic integration and globalization.