In recent years, umbilical cord blood (UCB) has emerged as a feasible alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack HLA-matched marrow donors. Since the first case reported in 1998, more than 3500 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 (UCBTs) have already been performed in adults. The "naive" nature of UCB lymphocytes also permits the use of HLA-mismatched grafts at 1-2 loci without higher risk for severe graft versus host disease (GvHD) relative to bone marrow transplantation (BMT) from a full matched unrelated donor. Furthermore, UCB is rich in primitive CD16(-)CD56++ NK cells, which possess impressive proliferative and cytotoxic capacities and can be induced to expand using IL-12 or IL-15, so as to mount a substantial graft versus leukemia (GvL) effect. The main disadvantage of UCB is the low stem cell yields, resulting in higher rates of graft failure as well as delayed time to engraftment compared to BMT. One rational approach to overcome this limitation involves ex vivo expansion of UCB derived hematopoietic precursors. In this review we tried to answer the question: UCBT how, when and for whom. This procedure is mostly applicable for children and especially those with indication for full allogeneic transplantation but who lack a matched sibling donor. Experimental approaches including ex vivo expansion of CB with cocktail of hematopoietic growth factors, with or without differentiation blocking agents, co-transplantation of haploidentical and CB cells or co-transfusion of CB and mesenchymal cells may enable successful UCBT in adults and probably will result in expanding the indication to solid tumors or autoimmune disorders.