From the first studies performed by Broxmeyer and his group, in the late 1980s, evidence was presented indicating that hematopoietic progenitor cells from human umbilical cord blood (UCB) possessed certain in vitro biological features that differed from those observed in their adult counterparts. Throughout the past 20 years, these observations have been confirmed and expanded by several groups, using both in vitro and in vivo models. Today, it is widely recognized that stem and progenitor cells present in UCB are biologically different from those present in adult marrow or peripheral blood. As compared to cells from adult subjects, UCB-derived hematopoietic cells possess higher proliferation and expansion potentials, and their capacity to self-renew is also superior to that of adult cells. Although the mechanisms responsible for such biological differences are still not fully understood, telomere dynamics, cell cycle progression, certain transcription factor pathways, differential gene expression, and the autocrine production of particular cytokines are some of the mechanisms that have been implicated. Understanding, at the cellular and molecular levels, the biological differences between neonatal and adult hematopoietic cells has a 2-fold relevance. On the one hand, it will help to understand and characterize basic principles and mechanisms involved in human developmental biology; on the other hand, it will help to gain a deeper knowledge on the biology of hematopoietic cell transplants and to improve and optimize such a clinical procedure.