At this time, methotrexate and CNS radiotherapy used together offer the best chance for prolonged remissions in children who develop overt CNS leukemia. Toxicity is a major problem. Unless a lower dose of radiation is used, the contribution of radiotherapy to neurotoxicity cannot be reduced. However, the toxicity of intrathecal methotrexate can be reduced by using Elliot's B as a diluent, combining methotrexate with hydrocortisone, and using a standard dose after the age of 3 years rather than a dose based on body surface area.Fortunately, the incidence of CNS leukemia has decreased over the years due to prophylactic CNS therapy. However, when a CNS relapse does occur, it carries a grave prognosis and is therefore still a significant problem necessitating continued research.