Purpose of Review: This review provides a concise summary of significant research progress on SIRT1 deacetylase in leukemia in the past year. SIRT1 is a multifunctional protein and recent studies demonstrate that SIRT1 plays a crucial role in myeloid leukemogenesis and drug resistance. RECENT FINDINGS: SIRT1 expression is typically low in normal adult hematopoietic stem/progenitor cells, but is increased in the leukemic stem/progenitor cells of chronic myeloid leukemia (CML). SIRT1 activation is mediated in both BCR-ABL tyrosine kinase-dependent and independent manners. SIRT1 activation promotes resistance of CML stem cells to tyrosine kinase inhibitors and acquisition of BCR-ABL mutations for acquired resistance. SUMMARY: On the basis of current findings, SIRT1 inhibition in combination with BCR-ABL tyrosine kinase inhibitors can be explored as a novel approach to eradicate leukemic stem cells and residual disease in chronic phase CML. SIRT1 inhibition may also help prevent acquired resistance through genetic mutations of advanced phases of CML, and extend remission. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.