Markers of the glutamatergic and GABAergic phenotypes coexist in developing hippocampal granule cells, and activation of these neurons produces simultaneous glutamate-receptor-mediated and GABA-receptor-mediated responses in their postsynaptic cells. In the adult, markers of the GABAergic phenotype and the consequent GABAergic transmission disappear but can be transiently expressed in an activity-dependent manner. Coexistence of glutamate and GABA in neurons from other regions of the brain is being discovered, and the possibility of these neurotransmitters being co-released gives the CNS a powerful computational tool. Although waiting to be confirmed by paired recordings, the hypothesis that glutamate and GABA are co-released from single cells is a valuable heuristic proposal in understanding the plasticity inherent to neuronal communication.