Publisher Summary The central nervous system's (CNS) innate immune response involves intricate signaling circuitry and cellular networks. The primary cells involved in neuroinflammation are the microglia that actively survey the brain micro­environment and upon activation, serve as the resident macrophages in the CNS. Microglia is derived from the bone marrow, and takes up residence in the brain during development, and comprises approx­imately 12% of the cells of the CNS. Microglia functions as a major immune mediator in the CNS and performs the func­tions necessary for recruitment of the immune system. In the mature CNS, microglia are apparently dormant (resting microglia) but are actively monitoring the environment, con­tributing to the maintenance of neurovascular integrity to prevent access of potentially damaging immune system ele­ments, and mitigating inflammation. The phagocytic role of microglia is displayed during early embryonic brain development in which the microglias ingest cellular debris of excess neurons that have undergone programmed cell death. Microglia are involved in multiple sclerosis, Alzheimer's disease, Parkinson's disease, HIV dementia, retinal degenera­tive diseases and many other conditions.