The control of severe infectious complications by preventive strategies, early diagnosis of infections and empiric broad-spectrum antibiotic therapy contributed to a marked improvement of survival in children with cancer over the last 20 years. This article overviews of the importance of prevention of infectious complications in immunocompromised pediatric patients with hematologic or oncologic diseases. The particular challenge of this age group with respect to the acquisition and the spread of pathogens, the spectrum of causative microorganisms and the principal issues of anti-infectious prophylaxis are considered.