Central nervous system cancers or exposure to CNS-directed therapies increase risk for neuropsychological deficits. There are no accepted guidelines for assessment of neuropsychological functioning in this population. A multifaceted literature search was conducted and relevant literature reviewed to inform the guidelines. Studies of neuropsychological outcomes are widely documented in the pediatric oncology literature. There is strong evidence of need for neuropsychological assessment, but insufficient evidence to guide the timing of assessment, nor to recommend specific interventions. Children with brain tumors and others at high risk for neuropsychological deficits should be monitored and assessed for neuropsychological deficits. Pediatr Blood Cancer 2015;9999:1–52. © 2015 Wiley Periodicals, Inc.