The fundamental principles of cortical organization and its development, postulated by Santiago Ramón y Cajal at the turn of the century, based on his exquisite observations and ingenious interpretation of neuronal assemblies impregnated with the Golgi method, are being expanded with the application of advanced methods of anatomy, molecular biology and genetics. In this chapter, I will focus on the concept of columnar organization and areal specifications of the cerebral cortex that has served as a useful framework for understanding its development as well as its function as an evolving organ of thought.