Although impressive biologic advances have increased understanding of leukemogenesis, we know little about the causes of the acute leukemias. Epidemiologic studies have focused primarily on children. Higher birth weight is associated with an increased risk of childhood acute leukemia. Several theories have been advanced that may account for these observations, and additional biologic studies are needed. Some epidemiologic studies suggest that the acute leukemias in children may have an infectious component. Again, further work, especially in the area of specific causative agents, is necessary. Another area for future epidemiologic study includes investigation of exposure to natural and synthetic DNA topoisomerase II inhibitors. Preliminary evidence suggests that exposure to these agents, which are found in certain foods and medications, may be related to the subsequent development of acute leukemia in infants. Curr Opin Oncol 1999, 11:20–24