The authors focus on the current differentiation of the world and on its cognitive, application and educational frameworks and importance for the present. Macro-regional differentiation of the world has resulted from geographic concepts and it is a foundation for understanding the global development of society. This article evaluates the specific concepts and factors that form concepts of world macro-regions prepared by famous authors. It also presents a methodological approach for macro-regional forming of the world. After a theoretical and methodological introduction there is a discussion of the differentiation of the world entitled “Macro-regional differentiation of the world – formation and application.” The authors also present their conception of world differentiation and evaluation of the creation macro-regions and their positive and negative influence of the macro-regional differentiation of the world.