Blood component transfusion is an integral part of the care of children with oncologic and hematologic conditions. The complexity of transfusion medicine may however lead to challenges for pediatric hematologists/oncologists. In this review, three commonly encountered areas of transfusion medicine are explored. The approach to the investigation and management of suspected platelet refractoriness is reviewed. The unique transfusion related challenges encountered by children undergoing stem cell transplantation are also discussed. Finally, issues arising out of the care of children with hemoglobinopathies are explored, with an emphasis on the incidence of allo- and autoimmunization. Pediatr Blood Cancer 2012; 58: 1106–1111. © 2012 Wiley Periodicals, Inc.