The proteoglycans are multifunctional macromolecules composed of a core polypeptide and a variable number of glycosaminoglycan chains. The structural diversity and complexities of proteoglycan expression in the developing and adult Nervous System underlies the variety of biological functions that these molecules fulfill. Thus, in the Nervous System, proteoglycans regulate the structural organisation of the extracellular matrix, modulate growth factor activities and cellular adhesive and motility events, such as cell migration and axon outgrowth. This review summarises the evidences indicating that proteoglycans have an important role as modulators of neurite outgrowth and neuronal polarity. Special emphasis will be placed on those studies that have shown that proteoglycans of certain subtypes inhibit neurite extension either during the development and/or the regeneration of the vertebrate Central Nervous System.