Recent reprogramming studies indicate that mammalian, somatic cells have the potential to achieve pluripotent states and undergo cell type switching. Such cellular traits are observed under natural conditions in animals that regenerate complex organs. A number of invertebrates display the amazing trait of whole body regeneration. Underlying this trait is the maintenance of pluripotent cells in somatic tissue, and molecular studies indicate the use of common players associated with pluripotency and germ cell properties between these invertebrates and mammalian pluripotent cells. In regenerative vertebrates, heart regeneration, lens regeneration, and retinal regeneration provide good examples of dedifferentiation and transdifferentiation. The molecular factors associated with these phenomena are discussed.