Brain abscesses in children with leukemia or other malignancies are rare and potentially fatal. We report on four children who developed brain abscesses during treatment for acute lymphoblastic leukemia (ALL). All patients received multimodal broad-spectrum antibiotic therapy and liposomal amphotericin-B in combination with hyperbaric oxygen. First-line antimicrobial treatment was modified when a causative organism was isolated. All four patients survived, with two patients showing complete resolution of neurological and MRI abnormalities and with two patients still having residual lesions. To date, all patients are in remission with three patients still receiving antileukemic therapy. Brain abscesses can be successfully managed by a multimodality approach even in severely immunocompromised cancer patients.