ALL survivors treated with chemotherapy alone remain at elevated risk for neurocognitive impairment. We used fMRI to investigate associations between clinical risk factors, neurocognitive performance and brain activity in survivors of ALL. Ninety-two survivors completed Verbal and Object N-back tasks during fMRI at end of therapy. Measures of working memory were completed as part of a neurocognitive evaluation. Working memory-related brain activation was associated with important clinical risk factors and neurocognitive performance. The pattern of behavioral and imaging responses provides evidence for both compromised and compensatory changes in regional brain function. fMRI may help in selecting patients for remedial intervention.