Treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a major therapeutic challenge. Systemic drug administration is the current treatment of choice, but patients often do not respond beneficially to this approach. Intrathecal (IT) drug administration has several anatomic and pharmacodynamic advantages over conventional systemic treatment of cerebral vasospasm. We reviewed the most recent literature describing IT administration of several drugs to treat aneurysm-induced SAH and cerebral vasospasm, including 16 clinical trials using IT fibrinolytic agents and 10 trials using several IT vasodilators. We evaluated the safety and effectiveness of these trials but made no attempt to perform a meta-analysis using these data. IT drug administration of fibrinolytic agents and vasodilators caused lysis of the subarachnoid clot burden and diminished cerebral vasospasm, respectively. The studies reviewed reported a wide range of drug doses, intervals between aneurysm hemorrhage and initiation of treatment, success of clot dissolution, and degree of vasodilation of vessels in vasospasm. Treatment of vasospasm by IT drug administration is safe and largely effective after the aneurysm has been secured. Our findings indicate that IT treatment effectively delivers a higher drug concentration to vessels in vasospasm with minimal systemic effects. Drugs administered by this route are reported to lyse subarachnoid clots, attenuate cerebral vasospasm, improve clinical outcomes, and decrease the incidence of hydrocephalus. With greater understanding of drug pharmacodynamics, the IT route of drug administration may provide a rational, alternative approach to treating aneurysm-induced cerebral vasospasm.