Multimodality therapies that include surgery, chemotherapy, radiotherapy, and various newer forms of targeted therapies have been commonly applied in childhood cancers. Such modalities are associated with complications that may adversely affect the outcome of cancer treatment. Acute complications that require surgical management form the focus of our discussion. These patients are often compromised by immunosuppression, thrombocytopenia, and malnutrition. The complications discussed include typhlitis, invasive aspergillosis (IA), pancreatitis, hemorrhagic cystitis, gastrointestinal hemorrhage, necrotizing skin and soft-tissue infections, and perianal infection. Familiarity with the spectrum of complications and their appropriate management approaches will minimize the patients' morbidity. Pediatr Blood Cancer 2012;59:405–409. © 2012 Wiley Periodicals, Inc.