Critical illness polyneuropathy (CIP) may aggravate sepsis and multiorgan dysfunction in pediatric oncology patients characterized by quadriparesis and difficult weaning from mechanical ventilation. Here, we report on an adolescent patient with acute lymphoblastic T-cell leukemia who developed critical illness neuropathy after an episode of sepsis with need for mechanical ventilation and intravenous catecholamines. Differential diagnoses like vincristine-induced polyneuropathy, anterior lumbosacral radiculopathy (ALR), Guillain–Barré syndrome, and chronic inflammatory demyelinating polyneuropathy — all occurring in pediatric patients with acute leukemia — are discussed. Pediatr Blood Cancer 2010; 54:161–165. © 2009 Wiley-Liss, Inc.