Unlike most bodily organs, the central nervous system (CNS) exists behind a blood–tissue barrier designed to minimize the passage of cells and macromolecules into the neural parenchyma. Yet, the CNS is routinely and effectively surveyed by the immune system. This review examines the mechanisms and participants in this immunological surveillance mechanism. The nature of the healthy blood–brain barrier, factors modifying it, and its central position in determining the number and nature of leukocytes permitted to enter, are considered. In addition the role in surveillance played by lymphatic drainage, migrating T and B lymphocytes, and elements of the monocyte/macrophage/microglia family are considered. While all these participants are known to be important in responding to a CNS antigen and/or establishing a site of inflammation in the nervous system, they also are major elements in maintaining the homeostasis of the CNS and permitting the necessary immunological surveillance of that organ. GLIA 36:118–124, 2001. © 2001 Wiley‐Liss, Inc.