Lifelong hematopoiesis is sustained by a very small number of hematopoietic stem cells capable of self-renewal and differentiation into multiple hematopoietic lineages. The sialomucin CD34 has been, and is currently, used for the identification and purification of primitive hematopoietic progenitors. Depending on the source of stem cells, CD34 may not be expressed on all progenitor cells. An alternative stem cell marker is prominin-1 (CD133), which is expressed on a subpopulation of CD34(+) cells as well as on CD34(-) progenitor cells derived from various sources including fetal liver and bone marrow, adult bone marrow, cord blood, and mobilized peripheral blood. CD133(+) stem cells can reconstitute myelo- and lymphopoiesis of lethally irradiated mice, and the characterization of the CD133 expression on stem cells provides some insights into the biology of the hierarchy and functional organization of human hematopoiesis. The availability of methods for clinical large-scale isolation of CD133(+) cells facilitates their use in autologous and allogeneic hematopoietic stem cell transplantation and possibly in other fields of regenerative medicine.