The successful treatment of acute myeloid leukemia (AML) is hampered by the development of chemotherapy resistant disease. One molecular mechanism of pleiotropic resistance, typical multidrug resistance (MDR), has been recognized as an independent adverse prognostic factor in AML. Therefore, uniform laboratory assays are needed to evaluate the effect of MDR expression on the clinical outcome of strategies to overcome resistance. One approach has been to administer high-dose therapy with stem cell support. In elderly patients, less toxic treatment is required, while the results of induction treatment in this age group need further improvement. The use of hematopoietic growth factors may reduce treatment-associated morbidity and mortality, but does not consistently enhance cell death. MDR reversal with cyclosporin or PSC833 has shown promising results in Phase I/II trials.