Stem cells are multipotent cells that have the ability to self-renew and differentiate. As a scientific and clinical entity, stem cell biology holds enormous potential for our understanding of biological systems and the resultant clinical applications. Stem cells persist in organisms throughout their lifespans, though they are usually found in rare numbers in adult tissues. It is now possible to create alternative sources of stem cell potential beyond the native stem cell pool, as cells without stem cell potential can be transformed into pluripotent stem cells by transferring specific gene combinations. In tissues with high turnover, like blood, stem cells continuously produce new cells. Given this immense proliferative potential and the importance of this process for organismal survival, stem cell regulation is necessarily extensive and complex. Much of this regulation occurs in specialized sites known as stem cell niches. The field of hematopoiesis has been the most successful in harnessing stem cell potential, and hematopoietic stem cells have become part of routine clinical care. Additional tissue stem cells have been identified, and clinical potential is broadening. We will provide a background for the concepts necessary for the evaluation of the clinical potential of stem cells in clinical application.