This is a clinical practice guideline for the empirical management of fever and neutropenia (FN) in children with cancer, and those who have received hematopoietic stem-cell transplantation (HSCT). The guideline examines initial presentation, ongoing management, and empirical antifungal therapy. Topics of interest include risk stratification to define patients with high-risk invasive fungal disease (IFD), recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and empirical antifungal therapy in IFD low-risk patients with prolonged FN.