This chapter talks about the cultural-historical approaches developed by Lev Vygotsky and Luria in contemporary neuropsychology. Systemic-dynamic Lurian analysis of the working brain is based on the Vygotskian concept of higher mental functions. The chapter focuses on cross-cultural neuropsychological research, neuropsychological aspects of illiteracy, and culture-related aspects of interhemispheric integration and the interaction of neurobiological and socio-cultural systems. Structural and functional imaging studies have shown that the development of new skills or the strengthening of previous ones is associated with brain reorganization. Vygotsky stated the problem of differences in new language learning between children and adults and concluded that they use different learning strategies. Today, cultural-historical approach seems self-evident that neuropsychological analysis must necessarily take into account cross-cultural similarities and differences. Cross-cultural neuropsychology has become one of the most promising research and clinical areas in the twenty-first century.