Cell adhesion molecules (CAMs) play important roles in cell-cell and cell-extracellular matrix interactions in both mature and developing nervous system. During development, they are involved in cell migration, axon guidance, target recognition, and synapse formation; while in the mature nervous system, they maintain synaptic connections, cell-cell contacts, and neuron-glial interactions. Injuries to the nervous systems break the stable state of the tissues and the repair of damaged tissues and regeneration of axons require the participation of CAMs both as adhesion molecules and as signal transduction molecules. One group of the well-studied CAMs in the nervous system is the immunoglobulin superfamily including L1 and neural cell adhesion molecule (NCAM). This review will be focussed on the involvement of L1, NCAM, and polysialylated NCAM in neural repair and axon regeneration after nerve injury and their potential applications in the treatment of CNS injury.