Chondroitin sulfate proteoglycans (CSPGs), including neurocan and phosphocan, are believed to be major components of brain extracellular matrix that interact with other matrix proteins and cell surface receptors. In addition, several brain CSPGs such as receptor protein tyrosine phosphatase beta are expressed as cell surface receptors that interact with proteins in the extracellular matrix and with receptors on neural cells. Recent in vitro studies demonstrate that, although the brain CSPGs neurocan and phosphocan can promote transient adhesion of neuronal cells, they inhibit stable cell adhesion and neurite growth promoted by the cell adhesion molecule Ng-CAM/L1. Neurocan and phosphocan bind with high affinity to Ng-CAM/L1 and N-CAM which may be their major receptors on neurons. These CSPGs also bind to other adhesion molecules, such as tenascin-C, and can differentially modulate adhesion of glia of tenascin-C. Both the glycosaminoglycan and the core glycoproteins contribute to the function of the brain CSPGs. When expressed in regions containing low levels of adhesion molecules, various CSPGs including phosphocan, neurocan, versican, aggrecan, and NG2 proteoglycan may act as barriers to cell migration and axonal growth. In regions containing high levels of adhesion proteins, brain CSPGs may still act to maintain certain boundaries while allowing selective axonal extension to proceed. There are numerous regions of overlap in the expression patterns of CSPGs and adhesion molecules in vivo, and the relative levels of these molecules as well as the organization of the extracellular matrix may be important factors that regulate the rate of axonal growth locally. Differential expression of CSPGs may be important for modulating cell adhesion as well as axonal growth and guidance during neural development, and continued expression may prevent these processes in the normal nature nervous system as well as following brain injury.