The central nervous system (CNS) requires an intact and peculiar environment in order to function properly. This homeostasis is maintained by the blood-brain barrier, which separates the CNS from the peripheral circulation. The ability of the CNS tissue to counteract the pathogenic effect of infectious agents is poor, because immune cells and humoral factors have no free access into the brain due to the formation of tight junctions by cerebral endothelial cells. In addition, under normal conditions the low expression of histocompatibility antigens, adhesion molecules, and immune mediators renders the CNS refractory to immune responses compared with peripheral organs. In addition, once inflammation within the nervous system occurs, it is difficult to control. Although inflammatory events are aimed at defending the CNS from pathogens and repairing lesioned tissue, they can also be deleterious by contributing to tissue damage and impairment of neurologic functions. Abundant research activity in this field has revealed that resident cells of the nervous system actively participate in intracranial immune defense by releasing inflammatory mediators able to regulate, neuronal functions in addition to immunological functions. The dichotomy of neuroinflammation is discussed in this review article, which reports diverse examples of chronic and acute diseases of the CNS in humans as well as in animal models.