Aim. In this paper we present a review of the main features of the extracellular matrix (ECM) of the central nervous system (CNS). Development. Proteoglycans (PG) are glycoproteins, a very common type of protein in the ECM. Among the PG, the most abundant type is the hyalectan or lectican family. The PG is formed by two main components; a protein and a sugar chain, which that is termed glycosaminoglycan (GAG). These GAGs are polymers of two simple sugars. The hyalectan family has GAGs of the Chondroitin sulphate type (CS), and for this reason they are termed PG-CS. PG-CS are linked to the hyaluronic acid (HA) and other molecules of the ECM in order to form a three-dimensional network. This network has several important roles in the maintenance of the homeostasis of the CNS. Conclusions. Several hypotheses have been proposed to elucidate the failure of the CNS regeneration after an injury or in several pathologies. It has been suggested that PG-CS, which expression is up-regulated after CNS injury, may play some role in this process of inhibition of the CNS regeneration. Furthermore, we present an approach to the therapeutic potential of the CNS regeneration after the inactivation of the PG-CS up-regulation.