We review research on the neuropsychological effects that central nervous system (CNS) cancer treatments have on the cognitive abilities of children and adolescents. The authors focus on the two most common malignancies of childhood: leukemias and brain tumors. The literature review is structured so as to separate out earlier studies, generally those published prior to 1995, as opposed to manuscripts that have been published within the past decade. This is an important distinction for both leukemia and brain tumors. Earlier studies were ground breaking in that they began to map out what could be expected in terms of intelligence and academic problems in survivors of pediatric malignancies. Survivorship in this population has and continues to markedly increase and this is largely due to changes in treatment protocols. Research on neurocognitive effects of disease and treatment in pediatric oncology has become increasingly sophisticated, and this literature review not only reflects this trend, but highlights the growing collaboration between neuropsychology, cognitive neuroscience, and neuro-imaging. Thus, our goal was to provide a historical foundation, lead the reader towards the progression of research methodology up to the current state of the art, and perhaps most importantly, discuss future directions. These directions are especially relevant to the concepts of remediation and treatment of cognitive problems, and this is emphasized at the conclusion of the review.