Nectins and nectin-like molecules (Necls) are immunoglobulin-like transmembrane cell-adhesion molecules that are expressed in various cell types. Nectins form homo- or hetero-trans-dimers in a Ca2+-independent manner, causing cell–cell adhesion. Their heterotypic binding is much stronger than their homophilic binding. In epithelial cells in culture, cell–cell adhesion complexes are formed by nectins first and then cadherins are recruited to the nectin-based cell–cell adhesion sites to cooperatively form adherens junctions (AJs). Recent studies have revealed that nectins in cooperation with cadherins are also involved in the formation of synapses. In this chapter, we first describe the roles and modes of action of nectins and Necls in epithelial cells and fibroblasts and then in the formation and remodeling of synapses.