The specification of neurotransmitter phenotype is an important aspect of neuronal fate determination. Substantial progress has been made in uncovering key extracellular signals and transcriptional regulators that control the mode of neurotransmission in several model systems, among which catecholaminergic and serotonergic neurons feature prominently. Here, we review our current knowledge of the regulatory circuits that direct neurotransmitter choice, and discuss the development of well-studied types of catecholaminergic and serotonergic neurons. One emerging concept is that different types of neuron use a similar core programme to control shared modes of neurotransmission, but recruit different factors that are specific for each neuronal type. Another is that most factors that specify neurotransmitter identity also control other features of the neuronal phenotype.