Glial cells form a structural and functional network with complex cell-cell communication pathways that enable fast and slow signalling amongst themselves as well as with neurons. They exert regulatory influence on normal synaptic transmission and alter it in disease. It is becoming increasingly clear that an understanding of brain function in disease conditions requires a better account of the highly plastic, disease-associated changes in glial physiology in vivo. Particularly, microglia, the brain's ubiquitous but normally inconspicuous immune effector cell, are prominently involved in many brain diseases. They respond rapidly and in a territorially highly confined way to subtle, acute and chronic pathological stimuli. Detection of microglial activation provides diagnostically useful formal parameters of disease, such as the accurate spatial localisation, disease progression and the secondary neurodegenerative or adaptive changes remote from the primary site of disease. The latter has potential relevance for the understanding of disease-induced brain plasticity. Systematic attempts are now undertaken, using positron emission tomography and a ligand with relative selectivity for activated microglia, to develop generic imaging tools for a cellular in vivo neuropathology.