Synapse assembly is the cellular mechanism that mediates the generation of physical connections between nerve cells and, thus, allows for the establishment of functional connectivity in the brain. The biogenesis of a synapse requires a set of highly coordinated molecular events, ranging from initial formation of adhesive contacts between an axon and a dendrite, followed by the recruitment and precise arrangement of synaptic organelles and proteins on both sides of the synaptic cleft, and culminating in the maintenance and remodelling of the exquisite architecture of a differentiated, i.e. mature, synaptic junction. Both the postsynaptic and the presynaptic compartment are thought to undergo stages of maturation that change and shape synaptic structure and function in a characteristic way. Recent evidence suggests that transsynaptic signalling, elicited by postsynaptic cell adhesion molecules, regulates the molecular events underlying presynaptic maturation. Thus, synaptic cell adhesion molecules, apart from physically connecting nerve cells, emerge as coordinators of presynaptic and postsynaptic differentiation across the synaptic cleft.