Regional Economics has just entered in its fifties. It is a young discipline compared to other branches of Economics, yet much work has been done in this field. A vast and rich number of theoretical and methodological approaches exist nowadays to incorporate space into logical schemes, laws and models which regulate and interpret the formation of prices, demand, productive capacity, levels of output and development, growth rates and the distribution of income in conditions of unequal regional endowments of resources. This contribution provides the state of the art in Regional Economics with the aim to highlight the scientific achievements obtained so far and the theoretical and methodological gaps which still need to be filled out. Aspects that run counter to general beliefs emerge by reading the original contributions of well-known theoreticians, and will be presented. Future challenges will emerge from a critical approach to the milestones achieved so far.