Umbilical cord blood transplantation is becoming an acceptable alternative source of hematopoietic stem cells for patients with malignant diseases. Cord blood differs from bone marrow and peripheral blood progenitors in its immune tolerance and kinetics of engraftment. In this article, we will review the biology of cord blood stem cells and clinical studies of cord blood transplants in pediatric and adult populations. We will also discuss potential uses of cord blood stem cells in regenerative medicine and novel methods for ex vivo expansion of hematopoietic stem cells. As we learn more about cord blood transplants, there is the potential to overcome the limitations of cord blood transplants so that they can become more widely available.