Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity.