The leukemias of infancy, characterized by an equal distribution of lymphoid and myeloid subtypes, account for 2.5-5% of the acute lymphoblastic leukemias (ALL) and 6-14% of the acute myeloid leukemias (AML) of childhood. Rearrangements of the MLL gene on chromosome 11q23 are the most common genetic abnormalities in both ALL and AML, occurring in 70-80% and approximately 60% of cases, respectively. Infants with ALL and a rearrangement of MLL typically present with hyperleukocytosis, massive organomegaly, CNS involvement, CD10- B-lineage phenotype and myeloid-associated antigen (CD15) expression. Prognosis in these cases is uniformly poor, whereas in similar cases without the genetic defect, it is good to intermediate. The presenting features of infant AML include monoblastic or myelomonoblastic morphology, hyperleukocytosis and extramedullary involvement. Expected outcome approximates that for ALL (approximately 30% long-term survival rate). Rare congenital forms of lymphoid or myeloid leukemia, manifested at birth or during the first month of life, carry a dismal prognosis, especially when a MLL/11q23 rearrangement is present; such cases should be carefully distinguished by chromosomal/molecular analysis and cell culture techniques from transient myeloproliferative disorders which require only supportive care but close follow-up for subsequent development of leukemia. Juvenile chronic myeloid leukemia also can occur in infants and may be responsive to chemotherapy alone. Rapid progress has been made over the past decade in understanding the biology of infant leukemias. The biggest challenge now is to develop more effective treatment, especially for patients with MLL rearrangements.