Leukemia was the first malignant condition in which cancer stem cells were described. Leukemia stem cells (LSCs) have now been described in a number of different types of leukemia and are currently a major focus of research interest. LSCs are an important target for treatment of leukemia, and failure to eradicate these very primitive cancer cells is a common cause of leukemia relapse. Therefore, improved understanding of the biology of LSCs and the differences between normal hematopoietic and leukemic stem cells is likely to lead to the development of novel therapeutic strategies and improvements in leukemia therapy and patient survival.