The unique groups of cell-adhesion proteins, such as IgSF, play essential parts in the formation and maintenance of the nervous system. Recent crystallographic studies have revealed a possible common structure of cell-adhesion proteins. The IgSF proteins are sub-grouped into simple, complex and mixed types. Accumulating evidence reveals the importance of cell-adhesion proteins in neural morphogenesis, maintenance and regeneration. They play key roles in neuronal migration, neurite outgrowth promotion, neurite fasciculation, pathfinding, target recognition, synaptogenesis and myelination. Mutations of cell-adhesion proteins result in neurological disease; for example, mutations of PO in hereditary neuropathy and mutations of L1 in hereditary hydrocephalus, MASA syndrome and spastic paraplegia type 1. Perspectives of the studies of neural cell-adhesion proteins are discussed.