Synaptic adhesion molecules have been extensively studied for their contribution to the regulation of synapse development through trans-synaptic adhesions. However, accumulating evidence increasingly indicates that synaptic adhesion molecules are also involved in the regulation of excitatory synaptic transmission and plasticity, often through direct or close associations with excitatory neurotransmitter receptors. This review summarizes recent results supporting this emerging concept and underlying mechanisms, and addresses its implications.