Recurrent chromosomal abnormalities present in the malignant cells of children with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) often correlate closely with specific clinical and biologic characteristics of the disease. Certain unique cytogenetic rearrangements are associated with distinct morphologic leukemic subtypes. These rearrangements should be detectable in most children with AML and MDS with the use of complementary molecular techniques such as fluorescence in situ hybridization (FISH), Southern blotting, and polymerase chain reaction. Apart from the diagnostic assessment, cytogenetic findings sometimes predict clinical outcome and thus also serve as prognostic parameters, which may affect the therapeutic decision. Alternative classifications of AML that take into account the genetic information are being proposed. Cytogenetic and molecular analyses may allow clinicians to more appropriately direct types of treatment. Abnormal fusion transcripts and chimeric proteins derived from karyotypic abnormalities now are being also targeted by novel therapeutic approaches.