The brain constitutes an environment that is specifically designed to accommodate, regulate and shape immune responses. On one hand, the central nervous system (CNS) has traditionally been regarded as an immunologically privileged organ, owing to local tissue barrier and immunosuppressive microenvironment. On the other hand, activated microglia and astrocytes express MHC and adhesion/costimulatory molecules, release reactive oxygen intermediates and cytokines, and participate in local immune regulation. Bidirectional interactions between immune and neuroglial components occur in response to infectious and traumatic lesions. Glial cells may facilitate and amplify immune effector mechanisms within the CNS. Cytokines and chemokines within the CNS constitute a specialized CNS-cytokine network, and regulate the development and recovery from autoimmune diseases within the CNS. The interactions between glial cells and lymphoid cells are constituents of a complex immune regulatory system within the CNS. New data on the cross-talk between the CNS and the immune systems are envisaged, and followed by an attempt to create a synthesis of current knowledge.