This chapter focuses on the evolution of regional innovation policies in the peripheral area of Apulia region in Italy. Despite the efforts of national and regional governments to improve its knowledge infrastructure, Apulia region’s research and innovation (R & I) system and policy are characterized by diverse strengths and weaknesses. The region shows structural constraints and has experienced sectoral crisis in traditional manufacturing that serves to impede its performance as an innovative region within the European context. A lower value of regional gross domestic product (GDP) and the relative fragmentation of research activities acts as barriers that slow the transformation of the regional system into a highly technological environment. Nevertheless, some areas of excellence such as the mechatronics and aerospace districts, the Information and Communications Technology (ICT) district, and start-ups are creating new opportunities and linkages between firms and knowledge infrastructure, as well as expanding R & I activities, in attempts to increase the rate of skilled human capital employed in local firms.