Low delivery of common chemotherapeutic drugs to the brain is considered to be a major obstacle for obtaining durable disease control in patients with high-grade gliomas. Intra-arterial drug injection after selective catheterization of cerebral arteries has been performed in some small clinical trials in order to achieve higher drug concentration in the tumor while minimizing systemic exposure. We reviewed the results in terms of response and toxicity from studies with intra-arterial administration of nitrosoureas and platinum derivatives, as well as the principal aspects and perspectives of the new strategy of blood-brain barrier disruption with osmotic agents or bradykinin analogs. No superiority of intra-arterial chemotherapy over its intravenous counterpart has been demonstrated so far and although the incidence of serious neurotoxicity is reduced, the risk of untoward acute complication still contraindicates internal carotid or vertebral artery catheterization for chemotherapy administration outside the setting of well-controlled clinical trials.