Cancer treatment, such as intrathecal chemotherapy and cranial radiation therapy, are frequently cited for their negative influence on neuropsychological functioning. Deficits have been noted in areas such as working memory, attention, IQ, and learning. The research reported herein used a multi-modal approach to explore the predictive value of inter-individual and treatment-related risk factors. In Study 1, I used a cross-sectional design to compare children treated for acute lymphoblastic leukemia (ALL) with a healthy control group for the association between predictive risk factors and deficits in verbal learning and memory, and IQ. In Study 2a, I analysed a longitudinal sample of individuals treated for pediatric ALL to explore changes in neuropsychological abilities over time, and evaluated their association with predictive risk factors. Finally, in Study 2b, I used the longitudinal sample from Study 2a to explore event-related potential components over time as a psychophysiological index of information processing, and the predictive risk factors associated with change over time. Treatment-related factors, such as chemotherapy protocol and total glucocorticoid dose emerged as significant predictors of impairment. The effects of radiation were more subtle than predicted. Sex, age at diagnosis, and indicators of parental well-being also predicted neurocognitive outcomes. This project filled a gap in the existing literature by answering specific questions about the nature of neuropsychological deficits following treatment for pediatric ALL, as well as helping to identify patients most at-risk for these impairments. To my knowledge, this is the first study to explore event-related potentials longitudinally in a pediatric cancer sample, and this technique may prove useful for tracking functional changes in neurocognitive function over time. The deleterious effects of treatment-related toxicity extend beyond neuropsychological performance and can impact all facets of everyday life, including personal distress and trauma, and costs to educational and healthcare systems and social infrastructure. These results may help clinicians identify patients who are most at-risk for developing neurocognitive impairments, and/or require modified treatment protocols, long-term monitoring, or early intervention.