Glutamate and GABA are the main synaptic neurotransmitters in the hippocampus. However, their actions are not limited only to the local postsynaptic zone. These amino acids can be released into the extrasynaptic space by glutamate and GABA reuptake, glial exocytosis, osmotic shock, and spillover (flowing out of the synaptic cleft). Glutamate and GABA receptors are also located on various parts of neurons and glial cells. Depending on the subcellular distribution of these receptors, their subunit composition, and the matabotropic/ionotropic functions, the effects of extracellular glutamate and GABA differ. The present review discusses the general principles of the organization of diffusion-based glutamatergic and GABAergic systems of extrasynaptic neurotransmission, the interaction of these systems with synaptic transmission, and the interaction of diffusion signals with each other.