The role of glial cells is to support and sustain proper neuronal function and microglia are no exception to this. This viewpoint article emphasizes the fundamental interdependence of microglia and neurons and takes a look at the possibility of what could happen if microglial cells became dysfunctional as a result of aging, genetics, or epigenetics. Could microglial senescence be a factor in the pathogenesis of Alzheimer's and other neurodegenerative diseases? The cautious answer to that question is ‘yes’. Future studies along these lines may provide novel insights into microglial involvement in neurodegenerative disease pathogenesis. GLIA 40:133–139, 2002. © 2002 Wiley‐Liss, Inc.