Unrelated cord blood transplantation has been used to treat patients with malignant and non-malignant hematopoietic disorders for whom an HLA-compatible hematopoietic stem cell donor is not available. The establishment of cord blood banks worldwide, the increased number of cord blood units frozen, and the shorter time to find a donor, have made it possible to use this source of hematopoietic stem cells to treat more than 2,500 patients. The Eurocord registry was established to study the clinical results of cord blood transplantation and to compare the outcomes of unrelated transplants using either cord blood or bone marrow. Briefly, we have found, in two distinct retrospective analyses of children or adults with acute leukemia given either an unrelated cord blood or bone marrow transplant, that leukemia-free survival and relapse were similar in both types of graft (with adjustment for confounding clinical factors). Cord blood recipients experienced a decreased incidence of acute graft-versus-host disease and delayed hematopoietic recovery compared to bone marrow recipients. To improve the delayed hematopoietic recovery after cord blood transplantation, certain approaches have been investigated such as ex vivo expansion of cord blood cells, double cord blood transplantation and reduced intensity conditioning regimen. We have also attempted to establish some guidelines for cord blood-donor choice based on cord blood cell dose and number of HLA disparities that have been found to be associated with hematopoietic recovery. In conclusion, an unrelated hematopoietic stem cell donor should be simultaneously searched for in cord blood banks and in bone marrow donor registries for patients lacking an HLA-identical sibling hematopoietic stem cell donor. The option of performing cord blood transplants should be based on urgency of the transplant, cord blood cell dose and number of HLA disparities.