Acute myelocytic leukemia (AML) is a heterogeneous disease that accounts for nearly a quarter of the pediatric leukemias. Despite near myeloablative therapy, half of patients relapse and die from their disease. Identification of patients at high risk of relapse early in the course of treatment may allow for treatment modification to improve their outcome. In addition, patients at lower risk of relapse may benefit from treatment de-escalation, sparing them adverse side effects. This review describes prognostic factors that play a major role in the outcome of children with AML and their potential use for treatment stratification in pediatric AML trials.