Predicting the outcome of therapy in patients with acute myeloid leukemia (AML) is currently necessary for making treatment decisions. Pretreatment covariates, such as clinical and molecular predictors, have helped identify which patients are more or less likely to survive their disease using the currently available regimens. Progress in establishing optimized flow cytometry and quantitative polymerase chain reaction assays for detecting minimal residual leukemia has provided new potential tools for predicting outcome. However, the most important next step in using these techniques toward personalized treatment of AML would be developing effective and safe strategies for eradicating the residual leukemic cells that are likely chemoresistant. With further refinement and standardization of the assays, and the development of novel, effective, and molecularly targeted agents, monitoring of minimal residual disease is likely to be incorporated into AML guidelines.