This chapter shows that Vygotsky-Luria's cultural-historical approach to neuropsychology is engaged with promises for many new discoveries that may lead to fundamental changes in our understanding of the human mind. Cultural-historical neuropsychology is an approach to studying higher psychological functions. Vygotsky-Luria's theory is based on the idea that specifically human higher psychological functions develop in the process of communication and material activity of a developing person in a socio-cultural environment. The chapter concludes that modern studies concentrate too much on single regions of the brain and/or on performance of isolated psychological tasks. Principles of systemic organization remain unrevealed by such studies. The developmental dynamics of the functional localization is even less well understood. The relation of the functional organization of the brain to the cultural environment needs to be studied.