Abstract: Drug resistance and relapse are two major causes for treatment failure of leukemia, but their mechanisms remain elusive. Recently, increasing evidence shows that there is a subset of leukemia stem cells apart from immature leukemia cells in leukemia patients. These cancer stem cells are not responsible to conventional chemotherapeutic agents, and may be the root of drug resistance and relapse of leukemia. Permanent cure of leukemia need elimination of these leukemia stem cells. We describe molecular characteristics of leukemia stem cells and possible target therapeutic strategies in this review.