AbstractA perineuronal net (PNN) is a layer of lattice‐like matrix which enwraps the surface of the soma and dendrites, and in some cases the axon initial segments, in sub‐populations of neurons in the central nervous system (CNS). First reported by Camillo Golgimore than a century ago, the molecular structure and the potential role of this matrix have only been unraveled in the last few decades. PNNs are mainly composed of hyaluronan, chondroitin sulfate proteoglycans, link proteins, and tenascin R. The interactions between these molecules allow the formation of a stable pericellular complex surrounding synapses on the neuronal surface. PNNs appear late in development co‐incident with the closure of critical periods for plasticity. They play a direct role in the control of CNS plasticity, and their removal is one way in which plasticity can be re‐activated in the adult CNS. In this review, we examine the molecular components and formation of PNNs, their role in maturation andsynaptic plasticity after CNS injury, and the possible mechanisms of PNN action. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 1073‐1089, 2011