The establishment of functional neural connections requires the growth of axons to specific target areas and the formation of synapses with appropriate synaptic partners. Several molecules that regulate axon guidance and synapse formation have been identified in the past decade, but it is unclear how a relatively limited number of factors can specify a large number of connections. Recent evidence indicates that transcription factors make a crucial contribution to the specification of connections in the nervous system by coordinating the response of neurons to guidance molecules and neurotransmitters.