During development of the nervous system following axon pathfinding, synaptic connections are established between neurons. Specific cell adhesion molecules (CAMs) accumulate at pre- and postsynaptic sites and trigger synaptic differentiation through interactions with intra- and extracellular scaffolds. These interactions are important to align pre- and postsynaptic transduction machineries and to couple the sites of cell-to-cell adhesion to the cytoskeleton and signaling complexes necessary to accumulate and recycle presynaptic vesicles, components of exo- and endocytic zones, and postsynaptic receptors. In mature brains, CAMs contribute to regulation of synaptic efficacy and plasticity, partially via direct interactions with postsynaptic neurotransmitter receptors and presynaptic voltage-gated ion channels. This chapter is to highlight the major classes of synaptic CAMs, their multiple functions, and the multistage concerted interactions between different CAMs and other components of synapses.