The conditions required for effective immune responses to viral or bacterial organisms and chemicals of exogenous origin and to intrinsic molecules of abnormal configuration, are briefly outlined. This is followed by a discussion of endocrine and environmental factors that can lead to excessive continuation of immune activity and persistent elevation of inflammatory responses. Such disproportionate activity becomes increasingly pronounced with aging and some possible reasons for this are considered. The specific vulnerability of the nervous system to prolonged immune events is involved in several disorders frequently found in the aging brain. In addition of being a target for inflammation associated with neurodegenerative disease, the nervous system is also seriously impacted by systemically widespread immune disturbances since there are several means by which immune information can access the CNS. The activation of glial cells and cells of non-nervous origin that form the basis of immune responses within the brain, can occur in differing modes resulting in widely differing consequences. The events underlying the relatively frequent occurrence of derangement and hyperreactivity of the immune system are considered, and a few potential ways of addressing this common condition are described.