Microglia cells are resident central nervous system (CNS) leukocytes that regulate innate immunity and participate in adaptive immune responses in CNS tissue. However, microglia cells also appear to play an important role during normal function of the mature nervous system. In response to injury, ischemia, and inflammatory stimuli, microglia cells assume an activated phenotype associated with proliferation, migration to the site of injury, phagocytosis of cellular debris, and elaboration (Power and Proudfoot 2001) of both neurotoxic and neurotrophic factors. Recent reports strongly suggest that regulating microglia function may be a fruitful future therapeutic target for the prevention of neurological dysfunction in a variety of CNS injuries and chronic diseases. Thus, developing a thorough understanding of extracellular signals that activate microglia as well as a complete catalogue of microglia responses to activating stimuli in both the healthy and diseased state are crucial scientific endeavors. This review presents the current understanding of the biology of microglia during normal CNS function as well as in response to CNS injury or neurodegenerative disease. In addition, microglia modulate both the activation and down-regulation of the adaptive immune response in the CNS. Evidence that microglia cells play a primary role in regulating CNS immune responses will also be discussed.