A major question of neurobiological research is how precise connections between neurons are formed and maintained. In the hippocampus, afferent fiber systems are known to terminate in a laminated fashion. Previous studies have indicated that this lamination is largely due to spatiotemporal constraints during ontogenetic development. In this commentary, recent fine structural studies on the target cell specificity of the various hippocampal afferents are discussed. It becomes obvious that some afferent fibers establish synapses with all available target cells, whereas other afferents are restricted to distinct types of neurons. A high degree of neuronal specificity is found in the hippocampal and dentate axo-axonic cells, which are restricted not only to specific types of target cells (pyramidal neurons and granule cells, respectively) but also to distinct portions of the target cell's membrane (the axon initial segment). Altogether, these data indicate that there are different levels of target cell specificity in the hippocampus. It is suggested that specific molecular interactions between pre- and postsynaptic elements, in addition to spatial and temporal factors, play a role in the formation and stabilization of the various synaptic connections of the hippocampal formation.