Circulating hematopoietic stem and progenitor cells play important roles in the physiology and homeostasis of the hematopoietic system. The frequency of these cells varies throughout development, being more abundant during gestation. In the adult, the numbers of such cells are extremely low; however, they can be increased by intravenous administration of chemotherapy and/or recombinant cytokines to individuals. This mechanism--known as mobilization--involves the disruption of the interactions between primitive hematopoietic cells and microenvironment elements (stromal cells and extracellular matrix molecules), which are mediated by a group of molecules known as cell adhesion molecules. During the last two decades, circulating cells of newborns (those present in umbilical cord blood) and adults (mobilized peripheral blood) have gained relevance not only because of their biology, but also because of their clinical application. Indeed, at present the number of mobilized peripheral blood-derived hematopoietic cell transplants performed worldwide is clearly superior to the number of bone marrow transplants being done annually. On the other hand, the number of cord blood transplants has significantly increased during the last few years, and cord blood banking has expanded in a significant manner over the last decade. Circulating stem and progenitor cells are being manipulated ex vivo, both in cellular and molecular terms, and the clinical use of these manipulated cells is just beginning. Undoubtedly, hematopoietic cells present in circulation will play a key role in the development of both gene and cellular therapies for a variety of diseases.