The central nervous system (CNS) can be invaded and damaged by a variety of microbes. The host response to such injury involves CNS cells, and in many cases hematogenous cells also. Recent experiments indicate that astrocytes, macroglial resident cells of the CNS, play key roles in this process. The astroglial production of trophic factors and elimination of neurotoxins are likely to fulfill important protective and reparative functions during CNS infection. In addition, astrocytes could, in concert with microglial cells, regulate the recruitment and activity of infiltrating hematogenous cells through their expression of cytokines, proteases, protease inhibitors, adhesion molecules, and extracellular matrix components. Although previous experiments suggested that astrocytes might initiate inflammatory demyelinating disease by presenting CNS antigens to autoreactive immune cells, current evidence points against such a detrimental activity. In view of the generally beneficial role of astrocytes, impairments of astroglial function by microbes or host-derived factors have the potential to contribute to neurologic disease. Diseases in which this pathogenetic process may be relevant include HIV-1-associated cognitive/motor complex and spongiform encephalopathies.