According to Lev Vygotsky, signs are understood as "artificial stimuli-means which are introduced by a human being into a psychological situation". This chapter discusses language, other sign systems and brain in the last studies of Vygotsky, in the works of Alexander Luria (particularly on aphasia) and in recent cognitive neuropsychology. The basic semiotic idea of Vygotsky consisted in the recognition of a sign and systems of signs as principal elements of all high psychic functions such as speech, writing, arithmetic, elaborated forms of attention and memory, control of behavior, culture as a whole system that comprises these subsystems. Vygotsky studied these functions as semiotic systems in their growth both from the point of view of the ontogenetic development of a child as well as from the phylogenetic side related to the world history of the culture of mankind.