The identification of molecular genetic alterations such as gene mutations or deregulated gene expression in acute myeloid leukemia (AML) has greatly advanced our understanding of leukemogenesis. These markers now allow us to unravel the enormous heterogeneity seen within cytogenetically defined subgroups of AML. Furthermore, the molecular alterations are providing targets for molecular therapies. In this article, major molecular findings of prognostic and predictive significance are reviewed, with an emphasis on the discussion of gene mutations found in two major AML subgroups, cytogenetically normal and core-binding factor AML.