In recent years much progress has been made in the understanding of the biology of hematopoietic stem cells (HSC) and their involvement in normal blood cell development. Using immunophenotyping it is possible, to enrich HSC, however, so far we are not able to positively select HSC. For the identification, characterization and quantification of HSC it is necessary to use functional assay systems, such as xenotransplantation models. HSC from bone marrow, peripheral blood and in some cases also cord blood have been used for years in transplantation settings especially in patients with leukemia. A better understanding of the mechanisms underlying stem cell regulation as well as stem cell self renewal would have clinical implications e. g. for clinical transplantation strategies. A number of hematological diseases such as chronic myeloid leukemia originates from a malignant transformed HSC. A better understanding of the biology of normal as well as malignant HSC is therefore crucial not only for a better understanding of the disease, but also for the development of strategies aiming at the discrimination of normal and malignant stem cell candidates and the development of therapies targeting the leukemic stem cell.