Reviewed 53 studies on the effects of central nervous system prophylactic treatment (CNSPT) on cognition and neuropsychological functioning. CNSPT involves irradiation and/or chemotherapy directed to the brain, and is frequently administered to children who have leukemia. The effects of CNSPT on neuropsychological functioning in long-term cancer survivors remains controversial. A number of studies failed to identify any neuropsychological impact secondary to CNSPT, whereas others reported deficits that appear to be a function of CNSPT. Several methodological issues that make it difficult to draw meaningful conclusions from this research literature are identified and discussed. Specific recommendations are made for improvements in research on CNSPT in children.