Abstract: The term microglia refers to the group of resident brain immune-cells that are responsible, mainly, for the immune response and the homeostasis of the brain. Unlike monocyte-derived macrophages that infiltrate the brain, microglia are long-lived cells which arise exclusively from the embryonic yolk sac (Stratoulias et al., 2019). Impairment in microglia functions is at the basis for the development of multiple brain diseases, including multiple sclerosis and neurodegenerative diseases. In the last decade, the number of research articles and reviews dealing with the role of microglia in the pathogenesis of brain disorders has exponentially increased. Indeed, microglia cells play a major role in both the brain homeostasis and the onset and maintenance of the inflammatory processes within the central nervous system (CNS) that often accompany the diseases. The complex mechanisms by which microglia exert their action in pathological conditions have not been completely clarified, yet, but their ability to mediate the intercellular communication with all of the other cell populations in the CNS tissue has clearly emerged in both physiological and pathological conditions (Paolicelli et al., 2018).