Introduction The acute leukemias of childhood are a heterogeneous group of diseases. In reviewing the descriptive and analytic epidemiology of these malignancies, we have emphasized specific subgroups, as defined by morphology [the French-American-British (FAB) classification], cytogenetic features, or molecular markers. There is evidence that specific subtypes of leukemia may have distinct etiologies, and that molecular abnormalities associated with particular subtypes may be linked with specific causal mechanisms. Moreover, the mutations produced at the successive stages of leukemogenesis, from initiation through induction to promotion, may all involve separate etiologic processes. It is also important to note that changes over time in diagnostic practice and precision may account in part for some reported epidemiologic trends. Moreover, changes in terminology and classification schemes for leukemia make it difficult to perform direct comparisons among studies, especially if risk factors differ for different subgroups. However, in assessing risk factors, studies of the childhood leukemias present several methodologic advantages. The interval between exposure to putative risk factors and the onset of leukemia may be shorter, recall of exposures is likely to be better, and intervening factors may be fewer than those associated with adult leukemias. These characteristics of childhood leukemia may facilitate identification of the most likely risk factors for each leukemia subtype. Furthermore, they lend themselves to an approach that includes both population studies and molecular epidemiologic techniques, permitting the design of research to assess genetic-environmental causal interactions.