Biological features of tumor cells relevant to progression, metastasis, and prognosis in cancer patients have been investigated for many years. During the past few years, the concept of tumor stem cells has gained widespread acceptance. The cancer stem cell (CSC) model is based on the observation that continuous growth of tumors depends on a small population of immature neoplastic cells with unlimited proliferative potential. In contrast to these CSC, more mature clonal cells in the same neoplasm undergo apoptosis and die after a variable number of cell divisions. The self-renewal capacity of CSC plays a central role in this scenario and enables permanent tumor cell repopulation in vivo in patients as well as in experimental animals, e.g., immunodeficient mice. Based on the stem cell concept, it is clear that the success of an anti-neoplastic approach depends on efficient targeting and elimination of CSC. An important aspect of CSC is their intrinsic resistance against conventional drugs. Therefore, a major focus in current research is molecular targets and their expression in CSC, with the goal to use targeted drugs for CSC elimination. It is the hope for the future that therapeutic approaches involving CSC-targeting concepts will lead to sustained remission and thus improvement of prognosis in leukemia and cancer patients.