Medical treatment for acute lymphoblastic leukemia (ALL) has improved survival rates to 70% for children currently diagnosed with this disease. Intrathecal (IT) chemotherapy replaced CNS radiation therapy (CRT) for those with a favorable diagnosis as research revealed cognitive deficits associated with CRT. The literature pertaining to the potential adverse intellectual and neurophysiological consequences of IT chemotherapy is reviewed. It is concluded that IT chemotherapy may not be a benign form of treatment, although its effects may be more subtle than those produced by CRT. Future studies implementing more comprehensive test batteries are needed to illuminate these deficits so that remediation may be possible for ALL survivors.