Simultaneous advances in stem cell and telomerase biology havegiven major insights into mechanisms that are central to bothleukemogenesis and stem cell-based therapies and biology. Aparadox is apparent in that both promotion and inhibition oftelomerase activity seem attractive therapeutic techniques,albeit in very different circumstances. For example, in vitrooptimization of telomere maintenance would be desirable duringstem cell expansion protocols, whereas an in vivo approach mightbe a rational therapeutic intervention in DKC. More excitingis the prospect of telomerase-directed therapeutics in cancer.A variety of strategies are being pursued (with some in earlyphase clinical trials), including immunization with hTERT peptidesand telomerase inhibition with modified oligonucleotides andhTERT-activated oncolytic viruses (recently reviewed in ).Such approaches may combine well with conventional leukemiachemotherapy, the latter to debulk the tumor and prevent earlydeath and the former introduced to inhibit telomere maintenance(and tumor regrowth) in the chemoresistant LSC population. Muchremains to be done, but hopefully a decade of impressive basicresearch will soon translate into therapeutic reality.