Microglia have long been ignored by neurooncologists. This has changed with the realization that microglial cells not only occur within and around brain tumors but also contribute significantly to the actual tumor mass, notably in astrocytic gliomas. In addition, it has been speculated that microglia could play a role in the defense against neoplasms of the nervous system. However, the biological success of these tumors, i.e., their highly malignant behavior, indicates that natural microglial defense mechanisms do not function properly in astrocytomas. In fact, there is evidence that microglial behavior is controlled by tumor cells, supporting their growth and infiltration. This unexpected “Achilles heel” of microglial immune defense illustrates the risk of generalizing on the basis of a single aspect of microglial biology. Microglia are highly plastic cells, capable of exerting cytotoxic functions under conditions of CNS infections, but not necessarily during glioma progression. Thus, the suggestion that microglial activation through stimulation by cytokines (e.g., interferon‐γ) will benefit patients with brain tumors could prove fatally wrong. Therapeutic recruitment of microglia to treat such diffusely infiltrative brain tumors as astrocytic gliomas must be considered premature. GLIA 40:252–259, 2002. © 2002 Wiley‐Liss, Inc.