Cancer is a multifaceted disease in which cell proliferation is no longer under normal growth control. Accumulating data have suggested the existence of cancer stem cells, a minor population of tumor cells that possess the stem cell property of self-renewal and that are responsible for the initiation and maintenance of cancer. The knowledge of cancer stem cell biology is most advanced in research on the hematopoietic cancer, leukemia. With the identification of leukemia stem cells (LSCs) capable of repopulating nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, this body of research has led to conclusive proof for cancer stem cells. This review focuses on the biological characterization of LSCs for each type of leukemia, which has provided key insights into leukemogenic pathology and LSC-targeted therapies.