Synaptic cell adhesion molecules are critical components of the molecular programs underlying synapse formation and neural circuit assembly. Here, we discuss our current understanding of the functional roles of several of these synaptic adhesion molecules in the mammalian central nervous system. Emerging evidence, driven by advances in super-resolution approaches, supports that pre- and postsynaptic machinery are highly organized at the nanoscale level and that these precise sub-synaptic positions are important for synaptic transmission. We subsequently describe the nano-organization of several synaptic cell adhesion molecules and how these trans-synaptic complexes align release machinery to shape the synaptic function. Collectively, an understanding of the mechanistic roles of synaptic cell adhesion complexes will provide insights into how neural circuits assemble by vast numbers of diverse synaptic connections in the brain.