During evolution from single-cell to multi-cellular organisms, organisms developed the needed machinery by which a vast number of functionally different types of cells could be unified into an individual. To attain this goal, organisms evolved the developmental strategies that produced different cell types and unified them into complex body architecture. However, a more intriguing feature of multi-cellular organisms is that they can maintain their bodies throughout long life. For tissue maintenance, stem and/or progenitor cells in many tissues and organs are thought to play an important role; however, we know little about their control and the process of tissue reconstitution. As cells are fragile, all animals have the ability, more or less, to replace damaged or dead cells; however, there are large variations in such abilities, depending on the type of organs and the species. Though vertebrates cannot reconstitute their bodies from a small piece as do planarians, some lower vertebrates, unlike mammals, have the ability to regenerate body appendages and many internal organs. If we unveil the nature of stem cells in striking examples of such regeneration, this information can be applied to mammals and greatly benefit us. The focus in the present review is on the recent advances in our knowledge about the regeneration mechanism in fish, including the stem cells that are involved.