Invasive fungal infections in children with cancer remain a challenging problem. Children receiving aggressive treatment are severely immunocompromised and thus highly susceptible to fungal infection. Because most studies investigating the incidence, mortality rate, and treatment of fungal infection in patients with cancer have been conducted in adults, this article will begin with an overview of data from the adult population. In pediatric patients, several cooperative group trials designed to identify the optimal chemotherapeutic regimens for children with hematologic malignancies have provided the opportunity to investigate invasive fungal infections in these patients. Data from study Children's Cancer Group (CCG)-2961 reported here include the incidence of infection, sites of infection, and infection-related mortality in children with acute myeloid leukemia. The two largest contributors to infection-related mortality in these patients were Aspergillus and Candida species. Another cooperative group study trial, CCG-2891, also involving children with acute myeloid leukemia, investigated the effects of intensity and type of cancer treatment on the incidence of fungal infection. Finally, a brief discussion of emerging fungal pathogens in pediatric patients with leukemia highlights 2 infections of growing concern: mucormycosis and scedosporiosis. Evidence indicates the need to more accurately identify these organisms and develop treatment protocols in immunocompromised children. (J Pediatr 2010; 156: S68-73).