The most impressive structural feature of the nervous system is the specificity of its synaptic connections. Even after axons have navigated long distances to reach target areas, they must still choose appropriate synaptic partners from the many potential partners within easy reach. In many cases, axons also select a particular domain of the postsynaptic cell on which to form a synapse. Thus, synapse formation is selective at both cellular and subcellular levels. Unsurprisingly, the nervous system uses multiple mechanisms to ensure proper connectivity; these include complementary labels, coordinated growth of synaptic partners, sorting of afferents, prohibition or elimination of inappropriate synapses, respecification of targets, and use of short-range guidance mechanisms or intermediate targets. Specification of any circuit is likely to involve integration of multiple mechanisms. Recent studies of vertebrate and invertebrate systems have led to the identification of molecules that mediate a few of these interactions.