Myelination of axons is a prerequisite for the rapid propagation of nerve impulses, and thus for the proper functioning of the nervous system. Phenotypic analysis of genetically engineered mice has provided evidence that cell adhesion molecules are critically involved in the interaction of myelin-forming glial cells with axons, the formation of regularly spaced myelin internodes along axons and the organisation of paranodes and the myelin-free gaps separating the internodes, the nodes of Ranvier. This review will focus on three members of the immunoglobulin-superfamily, the myelin-associated glycoprotein (MAG), the neural cell adhesion molecule (NCAM) and the neural adhesion molecule L1 and will discuss studies on transgenic mice that have analyzed the role of these cell adhesion molecules in the initiation of myelination, formation of structurally intact myelin sheaths and/or maintenance of myelin and axon integrity.