Microglia are one of the major glial cells in the brain implicated in the immune reactions in the central nervous system. Although the other major types of glial cells, astrocytes, oligodendrocytes and NG2 glia (or oligodendrocyte progenitor cells: OPCs) are all neuroectodermal cells, microglia are mesodermal macrophage-like cells. Because microglial cells have long been believed to be in the quiescent state in a normal mature brain, and to play no significant role, they have historically been called resting cells. However, it is currently accepted that such “resting” microglial cells with characteristic ramified morphology move their processes actively while surveying the microenvironment in the brain parenchyma. Still, the most prominent feature of microglial cells is their rapid activation in response to pathologic events including infection, inflammation, ischemia, trauma and neoplasms. Although microglia are normally neuroprotective cells, activated microglia in certain pathologic conditions are said to be a threat to neuronal survival by releasing potentially neurotoxic factors, such as glutamate, proinflammatory cytokines and reactive oxygen/nitrogen species, which aggravate neurological disorders by causing neuronal death. Microglial functions are affected by many kinds of endogenous substances such as neurotransmitters and corticosteroid hormones. Physical exercise may have the potential to suppress unfavorable activation of microglia in degenerative neurological disorders including Alzheimer’s disease and Parkinson’s disease by affecting neurotransmitters in the brain and serum level of the hormones.