Infections are an important cause of morbidity and mortality in children undergoing treatment for cancer. Up to two-thirds of toxic deaths during cancer treatment are caused by infections, which are especially lethal during intensive cancer therapy. In immunosuppressed pediatric patients, the etiology of infections ranges from common pathogens infecting their usual hosts to opportunistic microorganisms arising from the normal flora, from the reactivation of past infections, or from the environment. Risk factors that make immunosuppressed children vulnerable to infections include frequent breaches of the natural barriers of the body, alterations in innate and acquired immunity, the presence of foreign bodies, intensive medical care, and malnutrition. Infectious syndromes frequently seen in immunosuppressed children include febrile neutropenia, bacteremias, sepsis and septic shock, respiratory infections, skin and soft tissue infections, and alimentary tract infections. Infections may be caused by fungal, bacterial, viral, or parasitic pathogens, some of which exhibit multidrug resistance. Surgical site infections are potentially serious complications, and preventing these is of the upmost importance. They can be decreased by ensuring optimal preparation of the environment of care and appropriate conduct of the surgical procedures, including timely administration of prophylactic antimicrobials. Providers of care for children with cancer must have an excellent knowledge of the various types of malignancies, the risk factors for infections, and the causative pathogens thereof, together with awareness of the most effective antibiotics, the effects of drugs, and potential drug–drug interactions. This knowledge will enable care providers to manage the treatment of children with infections and cancer.