The brain is the most complex organ of the human body. It is composed of several highly specialized and heterogeneous populations of cells, represented by neurones (e.g. motoneurons, projection neurons or interneurons), and glia represented by astrocytes, oligodendrocytes and microglia. In recent years there have been numerous studies demonstrating close bidirectional communication of neurons and glia at structural and functional levels. In particular, the excitatory transmitter glutamate has been shown to evoke a variety of responses in astrocytes and oligodendrocytes in the healthy as well as the diseased brain. Here we overview the multitude of glutamate sensing molecules expressed in glia and describe some general experiments which have been performed to identify the glutamate-responsive molecules, i.e. the ionotropic and metabotropic glutamate receptors as well as the glutamate transporters. We also discuss a transgenic mouse model that permits detailed and specific investigations of the role of glial glutamate receptors.