Local invasion of the brain by neoplastic glial cells is a major obstacle to effective treatment of intrinsic brain tumors. Invasion is directly related to histologic malignancy, but occurs to some extent irrespective of tumor grade. Because the brain-to-tumor interface is not well demarcated, total surgical removal is rarely possible; moreover, as invading cells transiently arrest from cell division they are refractory to radiotherapeutic intervention. Invading cells may also be protected from the action of cytotoxic drugs by the presence of an intact blood-brain barrier. The invading cells, having migrated several millimeters or even centimeters from the main focus of the tumor, return to cycle phase under the control of some as yet unknown microenvironmental cue to form a recurrent tumor adjacent to the original site of presentation. Recent cellular and genetic information concerning factors underlying invasion may not only yield suitable targets for adaptation of existing therapies, but may also lead to novel approaches in glioma management.