The central nervous system has long been considered an immunologically privileged site. Nevertheless, cells derived from the bone marrow can and do enter the CNS in a number of circumstances. Derivatives of the monocyte/macrophage lineage appear to enter and take up residence in various structures of the CNS as part of normal ontogeny and physiology. Immunocompetent cells, such as T‐lymphocytes of both CD4 and CD8 positive groups, enter the nervous system in what appears to be a random fashion when they are activated by antigenic stimulation. These lymphocytes perform the required immunological surveillance of the CNS, and initiate inflammation therein during infectious and autoimmune reactions. In this review, the evidence supporting the above observations is examined, and a hypothesis for the pathogenesis of CNS inflammatory reactions is presented.