Stem cell transplantation (SCT) is an increasingly used therapeutic approach for the treatment of hematological and non-hematological disease of neoplastic and non-neoplastic origin. How the phenomena controlling blood cell production take place during SCT is still largely unclear. Increasing knowledge of stem cell biology, the availability of large amounts of stem cells due to mobilization techniques, as well as new developments in hematopoietic cell manipulation offer exciting experimental and therapeutical options in the field of SCT and will be reviewed here.