In recent years, umbilical cord blood has emerged as an alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack an human leukocyte antigen-matched marrow donor. Since 1998, about 2,500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg, however more than 500 UCB transplantations have already been performed in adults. The “naive” nature of UCB lymphocytes may explain the lower incidence and severity of graft versus host disease encountered in UCBT compared to the allogeneic transplant setting. Furthermore, UCB is rich in primitive CD16-CD56++ natural killer cells, which possess significant proliferative and cytotoxic capacities and can be expanded using interleukin-12 or 15, so as to mount a substantial graft versus leukemia effect. The major disadvantage of UCB is the low yield of stem cells, resulting in higher graft failure rates and slower time to engraftment compared to bone marrow transplantation. A rational approach thus involves ex vivo expansion of UCB-derived hematopoietic precursors.