Patients with acute myeloid leukemia and acute lymphocytic leukemia receive significant numbers of blood products for hematologic support during periods of disease and treatment related cytopenias. These patients may be at increased risk for complications associated with transfusion. This article reviews the indications for platelet and red blood cell transfusion, as well as the incidence and strategies for prevention of the immunohematologic and infectious sequelae arising in the setting of multiple blood component transfusions.