Despite steadily improving long-term outcomes, infections remain a major cause of morbidity and mortality in children receiving therapy for leukemia. Standardized approaches to the management of bacterial infections have been highly successful. However, management of fungal and viral infections remains challenging, especially given the shifting epidemiology of fungal infections. Significant advances in diagnostic and therapeutic modalities have been achieved for fungal and viral infections over the past decade, providing new opportunities for effective interventions. This article reviews the management of viral and fungal infections in children undergoing therapy for leukemia.