Infectious postoperative complications are common and significantly contribute to morbidity and mortality of surgical procedures in pediatric populations. Antibiotics can be given in the perioperative and postoperative period where they may be used either as prophylaxis or treatment. Pediatric oncology patients are at higher risk of postoperative infections compared to other pediatric surgical cohorts due to a combination of immunosuppression, long operation times, malnutrition, and high incidence of drains/indwelling devices. Antibiotic prophylaxis can reduce the incidence of surgical site infections when appropriate antibiotics are selected. Postoperative infectious complications that require antibiotic treatment include surgical site infections, line infections, pneumonias, and urinary tract infections. Antibiotics form an important part of the management of these complications, and appropriate antibiotic selection is key to the optimal management of the patient. Antibiotic therapy has risks including promoting antimicrobial resistance, C. difficile infection, and altering the gut microbiome – these risks must be weighed against the benefit of starting antibiotic therapy, especially in the case of prophylaxis antibiotic therapy where the benefit may be less clear. This chapter focuses on the principles of when antibiotic therapy is indicated, the appropriate selection and duration of antibiotics, and how these benefits should be weighed against the risks.