It is established that astrocytes are the intimate partner of neurons throughout their lifespan. However, astrocytes play different roles at different stages of the lifespan. During neurogenesis and early development, glial cells provide a scaffold for the correct migration of neurons and growth cones. They provide guidance cues and may also be involved in neuronal proliferation. In the adult, astrocytes maintain neuronal homeostasis and synaptic plasticity. This review discusses some of the cell-cell communication signals which are involved in the maintenance of synaptic plasticity. They are divided into: (a) glia-to-glia signaling, which involves non-synaptic communication by coupling of astrocytes. In this cell communication, cytoplasmic exchange of ions and small molecules among cells is accomplished through cell coupling of cells via cell-to-cell contacts, termed gap junctions; (b) neuron-to-glia signaling, which involves synaptic interactions. This cell-cell intercommunication has received considerable attention. Of special interest is the role of astrocytes in glutamic acid compartmentation and in preventing glutamic acid neurotoxicity. A glutamate-induced calcium signaling appears to be involved in this neuron-astrocyte interaction. The intriguing possibility is that neuronally induced astrocyte calcium signals may feed back to influence neuronal excitability or regulate synaptic transmission; (c) signals from astrocytes to neurons: a new concept of neuron-glia intercommunication. As mentioned, calcium appears to be the molecule in this glia-neuron signaling, although glial cell receptor-mediated signals are involved also. Receptor interactions on astrocytes through a cascade of events lead to modification in the extracellular concentration of glutamate. The role of astrocytes in synaptic plasticity is not as well understood during ageing and their role in neuronal cell death during ageing and neurodegeneration can only be speculated. However, astrocytes in the aged brain exhibit various receptors, including glutamate receptors. Thus, astrocytes can be expected to modify the expression of endogenous neurotoxins and thus contribute to synaptic plasticity in ageing. Synaptic plasticity continues to be a homeostatic relationship between neurons and glial cells. The possibility of signaling from astrocytes to neurons has opened new horizons for glial cell function and new challenges of research for gliobiologists.