Microglia, residential macrophages in the central nervous system, can release a variety of factors including cytokines, chemokines, etc. to regulate the communication among neuronal and other types of glial cells. Microglia play immunological roles in mechanisms underlying the phagocytosis of invading microorganisms and removal of dead or damaged cells. When microglia are hyperactivated due to a certain pathological imbalance, they may cause neuronal degeneration. Pathological activation of microglia has been reported in a wide range of conditions such as cerebral ischemia, Alzheimer's disease, prion diseases, multiple sclerosis, AIDS dementia, and others. Nearly 5000 papers on microglia can be retrieved on the Web site PubMed at present (November 2001) and half of them were published within the past 5 years. Although it is not possible to read each paper in detail, as many factors as possible affecting microglial functions in in vitro culture systems are presented in this review. The factors are separated into “activators” and “inhibitors,” although it is difficult to classify many of them. An overview on these factors may help in the development of a new strategy for the treatment of various neurodegenerative diseases.