Although relatively neglected previously, research efforts in the past decade or so have identified a pivotal role for glial cells in regulating neuronal function. Particular emphasis has been placed on increasing our understanding of the function of microglia because a change from the ramified “resting” state of these cells has been associated with the pathogenesis of several neurodegenerative diseases, notably Alzheimer’s disease. However, it is not clear whether activation of microglia and the associated inflammatory changes play a part in triggering disease processes or whether cell activation is a response to the early changes associated with the disease. In either case, the possibility exists that modulation of microglial activation may be beneficial in some circumstances, underlying the need to pursue research in this area. The original morphological categorization of microglia by Del Rio Hortega into ameboid, ramified, and intermediate forms, must now be elaborated to encompass a functional description. The evidence which has been generated recently suggests that microglia are probably never in a “resting” state and that several intermediate transitional states, based on function and morphology, probably exist. A more complete understanding of these states and the triggers which lead to a change from one to another state, and the factors which modulate the molecular switch that determines the persistence of the “activated” state remain to be identified.