Acute myeloid leukemia (AML) in adults is a heterogeneous malignant pathology with a globally unfavorable prognosis. The classification of AML allows identification of subgroups with favorable prognosis. However, besides these specific subgroups, most patients will have an intermediate or unfavorable prognosis often resulting in induction failure, probably due to drug resistance of the leukemic blasts, and more frequently resulting in early relapse after achieving complete remission. This unfavorable situation leads to a strong need to develop new diagnostic and therapeutic options. However, development of these therapies and their efficient use requires a better understanding of the biology and the molecular pathogenesis of AML. Pharmacogenomics focuses on the genetic variation of drug-metabolizing enzymes, targets and transporters, and how these genetic variations interact to produce specific drug-related phenotypes. Potential genetic markers may serve to functionally subclassify patients by their disease and therefore influence the nature and intensity of treatment. This review summarizes important aspects of and recent advances in the field of pharmacogenomics in AML.