Current medical treatments for childhood acute lymphoblastic leukemia (ALL) have improved the outlook to where more than 50% can be expected to survive five years or more. The use of CNS prophylaxis has contributed in a significant way to these improved survival statistics by reducing the likelihood of CNS relapses. The literature relating to the potential adverse psychological consequences of CNS prophylaxis, which include cranial radiation therapy (CRT), is reviewed and analyzed. The majority of published papers of children in first remission report that CNS prophylaxis, which include both CRT and intrathecal methotrexate, results in a variety of learning problems in many children who were younger than age 5 when treated. The available literature on the social, emotional, and educational sequelae of childhood ALL is also reviewed.