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2008 marks the 20th anniversary of the first use of umbilical cord blood (UCB) as a source of donor cells for hematopoietic stem cell transplantation. In those early days, there was great doubt and skepticism about the utility of UCB as a source of hematopoietic stem cells. Doubts about whether UCB, containing 10–20× fewer cells than bone marrow, had sufficient cells to durably engraft a myeloablated patient and, after demonstration that engraftment occurred with less graft-versus-host disease, whether it would confer graft-versus-leukemia activity were raised.Transplantation with UCB is effective in the treatment of children with hematological malignancies, marrow failure, immunodeficiencies, hemoglobinopathies and inherited metabolic diseases. Transplantation without full human leukocyte antigen matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia is preserved. The number of cells in a single UCB can be limiting, but the use of two UCBs for a single transplant shows promise to overcome this obstacle.Cord blood transplantation is now an established field with enormous potential. UCB increases access to transplantation therapy for many patients unable to identify a fully matched adult donor. In the future, it may emerge as a source of cells for cellular therapies focused on tissue repair and regeneration.