Infections of the central nervous system (CNS) are a common cause of neurological abnormalities in pediatric oncology patients apart from cancer disease of the CNS. Often symptoms do not present unequivocally, impeding a clear distinction from other differential diagnosis. Repeated neurological examinations of the patient allow selecting the necessary laboratory tests and imaging techniques. As delayed antiinfectious treatment is associated with high mortality and severe sequelae of survivors, patients do need empirical therapy using adequate doses until diagnostic results allow a more specific treatment. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of infections of the CNS in immunocompromised patients.