Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy on health outcomes. Neurocognitive late effects of chemotherapy occur in 40 - 60% of acute lymphoblastic leukemia (ALL) survivors. These deficits affect mental health, school performance, job success, and are associated with poor quality of life, therefore presenting a clinical challenge for psychiatrists. However, not all cancer survivors are impacted by treatment in the same manner and emerging evidence suggests that genetic variation may modulate neurocognitive outcomes. Much like other complex psychopathologies, neurocognitive deficits in cancer survivors are the result of complex interactions between genetic and environmental variables. This review describes adverse neurocognitive outcomes observed in survivors of acute lymphoblastic leukemia (ALL) and discusses genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributing to psychopathology in ALL survivors.