There never has been a more difficult time to advise patients newly diagnosed with chronic myeloid leukemia (CML). Until recently,the options comprised noncurative but relatively nontoxic chemotherapy or potentially curative allogeneic stem cell transplantation,with its attendant morbidity and mortality. There now is the additional option of the tyrosine kinase inhibitor imatinib mesylate that has been in clinical practice for almost 5 years. Although data are emerging regarding the efficacy of imatinib, solid evidence of any prolongation in survival will be delayed for several years. Future management of CML will continue to depend on a combination of approaches that use allografting and targeted drug therapy. The next decade undoubtedly will witness the introduction of a number of agents capable of inhibiting signal transduction pathways,perhaps controlling CML in cases of primary or acquired imatinib resistance. In the absence of long-term outcome data for imatinib,it remains reasonable to propose that young patients with newly diagnosed CML who have HLA-identical or well-matched unrelated donors should undergo allogeneic transplantation using a standard or nonmyeloablative conditioning regimen. Similarly,patients who fail to respond to imatinib should be rescued with a transplant strategy. The role of molecular monitoring in these two strategies cannot be underestimated.