As originally conceived, central neurotransmitters operated uniformly, exciting or inhibiting postsynaptic targets by receptors that activated passive ionic conductances. As the list of transmitter substances and their actions expanded, concepts of transmitter actions have broadened and grown more complex to include a variety of intramembranous and intracytoplasmic second messengers that can regulate both active and passive ionic conductances. Present-day research directions center on further expansion of the lists of identified transmitter candidates, and on the more precise characterization of their sites and mechanisms of receptor regulation and transduction. Current research is also illuminating the means by which neurotransmitters act in a coordinated fashion to regulate common synaptic targets. Future directions will likely include new forms of interneuronal, intraneuronal, and glial signals, including lipids, steroids, and as-yet-undiscovered superfamilies of peptides and receptors. Although recent advances in understanding specific transmitters have been achieved largely through in vitro electrophysiological analyses, it is hoped that future research will recast these events in the context of the intact functioning brain. Neurotransmitters are likely to remain a productive focus of future research.