Malignant gliomas confer a dismal prognosis. As the molecular events that underlie tumor angiogenesis are elucidated, angiogenesis inhibition is emerging as a promising therapy for recurrent and newly diagnosed tumors. Data from animal studies suggest that angiogenesis inhibition may promote an invasive phenotype in tumor cells. This may represent an important mechanism of resistance to antiangiogenic therapies. Recent studies have begun to clarify the mechanisms by which glioma cells detach from the tumor mass, remodel the extracellular matrix and infiltrate normal brain. An array of potential therapeutic targets exists. Combination therapy with antiangiogenic and novel anti-invasion agents is a promising approach that may produce a synergistic antitumor effect and a survival benefit for patients with these devastating tumors.