Synaptogenesis is a finely organized process, intriguing in its precise temporal and spatial resolution. It occurs as the dendrite of a postsynaptic neuron and an incoming axon communicate at defined sites to establish a stable synapse together. The molecular cues that guide synaptogenesis are now beginning to be identified, and cell surface interactions at synaptic sites participate prominently in the key steps. Interactions include trans-synaptic adhesion of pre- and post-synaptic neurons but also binding to non-neuronal neighboring cells and the extracellular matrix. These signals recruit scaffolding molecules, other adhesion molecules, and neurotransmitter receptors to bring together the key components of functional synapses. Recent progress provides stimulating insights into the role of adhesion and signaling molecules in the formation and function of synaptic specializations.