Recent progress in stem cell research is opening a new hope for cell therapy in regenerative medicine. Two breakthroughs were made in the stem cell era, one, new discoveries in multipotentiality of adult stem cells beyond the traditionally appreciated extent, and the other, establishment of pluripotent stem cell from human embryo. In addition to the newly identified multipotentiality of adult stem cells, their ability to be trans-differentiated toward other tissue types (stem cell plasticity) as well as to migrate toward the site of tissue damage make adult stem cells particularly attractive choice for stem cell based therapy. Stem cell therapy for organ regeneration, therefore, could be approached from three distinct dimensions: first, direct differentiation of multi-potent stem cells toward desired tissue types; secondly, regeneration of specific tissues through in vivo stem cell plasticity, and lastly, by tissue-specific stem cells from many types of organs. While each approach in stem cell therapy poses distinctive limitations for their success-ful clinical applications, understanding regulatory mechanisms of stem cell selfrenewal and their in vivo engraftment will mostly extend their medical efficacy of stem cell based therapy.