The stem cell story begins with the recognition of the regenerative powers of the head of the Lernean Hydra and the human liver (Prometheus) by the ancient Greeks. In modern times, the adult human stem cell has been epitomized by the hematopoietic stem cell in the bone marrow. More recently, bone marrow derived cells were reported to contribute to nonhematopoietic organs, suggesting a level of plasticity not previously expected. However, other reports failed to repeat some of these results, resulting in a heated debate on the plasticity of adult stem cells that has crossed over into the public domain and become a matter of political impact on the use of embryonic vs adult stem cells for organ regeneration or gene therapy. This review discusses the current status of the "plasticity" debate and presents existing data on detection methodology, underlying mechanisms, physiological implications, and clinical significance.