Owing to its easier accessibility and less severe graft-versus-host disease, umbilical cord blood (UCB) has been increasingly used as an alternative to bone marrow for hematopoietic stem-cell transplantation. Naiveté of UCB lymphocytes, however, results in delayed immune reconstitution and infection-related mortality in transplant recipients. This article reviews UCB immunology and addresses the potential therapeutic role of interleukin (IL)-15, a pleiotropic gamma chain signaling cytokine, in modulating immune reconstitution, graft-versus-host disease (GVHD), graft-versus-leukemia effect, and infection susceptibility during the post-UCB transplant period. Cytokine immunotherapy using IL-15 simultaneously modulates several immune compartments, thus holds promise for facilitating post-transplant recovery and augmenting antitumor effect without aggravating GVHD in the setting of UCB transplantation.