Immunological privilege of the central nervous system (CNS) has often been viewed as the summation of mechanisms that are protective of, but extrinsic to, the CNS. Their primary role has then been seen as isolating the CNS from the organism as a whole. Experiments in recent years indicate that the CNS itself may have an innate immune system comprised of astrocytes and microglia capable of regulating the initiation and progression of immune responses. Thus, immunological privilege should be considered as an intrinsic property of the CNS that could involve direct CNS: immune cell interactions. Malfunctions of these intrinsic mechanisms could play significant roles augmenting or even initiating CNS-directed autoimmunity and inflammation.