Large numbers of different proteoglycans are expressed in tightly regulated spatio-temporal patterns by both the nerve cells (neurons) and the supporting glial cells of the nervous system. Several of these proteoglycans have been shown by studies in vitro to affect the migration of neural precursor cells, the elongation and pathfinding of neurites and the formation and stabilization of synapses. Such processes are important for the accurate wiring of the nervous system, and so it has been postulated that proteoglycans play an essential role during neural development. However, with few exceptions, the phenotypes of null mutations in mice and some human genetic diseases have provided little support for this view. Here we will review recent data from both in vitro and in vivo studies analyzing the function of proteoglycans in the nervous system in order to provide possible explanations for their apparent lack of function.