Cord blood, donated by mothers after the birth of their children, has become an accepted source of related and unrelated hematopoietic stem cells for marrow reconstitution. We estimate that some 7-8000 unrelated-donor cord blood transplants have been performed worldwide since 1993. The development of cord blood as a source of hematopoietic stem cells for transplantation started with the early recognition of the presence in cord blood of colony-forming cells by Knudtzon in 1974. The first cord blood transplant from a human leukocyte antigen (HLA)-identical sib to a young patient with Fanconi anemia was performed by Gluckman in 1988 and opened the way for the subsequent development of a bank for donations for unrelated patients by our group at the New York Blood Center. It is now widely recognized that two transplant-dependent variables exert strong influence on the chance for long-term recipient survival: the hematopoietic stem and progenitor cell dose and the HLA match grade. Hence, despite the generally milder graft-vs-host disease after mismatched cord blood transplantation, large and ethnically diverse inventories of cord blood are needed to permit better HLA matches and long-term survivals. In this review, a number of issues that are relevant to the history and development of an effective system for cord blood banking are discussed.