This chapter critically reviews the emergence and evolution of Regional Science as an academic discipline for more than the last five decades. For assessing the role of the discipline in hosting the scholarly output, the Scopus Source List 2019 is used. It examines the constraints in Regional Science practices in taking an influential role to disseminate innovative ideas concerning regional planning and assesses its prospects in getting reinstalled at the core of regional and spatial planning strategies. The chapter ends with a critical discussion on why the socially and economically transforming Global South could be an interesting field of investigation for the practitioners of Regional Science.