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The regenerative phenomenon is widespread, but regenerative capacity varies greatly across animals. Invertebrates and phylogenetically primitive vertebrates, such as salamanders and zebrafish, often possess a higher regenerative capacity than mammals have. Even in the same individual, different tissues or organs exhibit distinct regenerative capacity; for example, livers regenerate more readily than hearts in mammals. In addition, the younger animal is usually easier to regenerate than the older. Decades of research are beginning to yield explanations about why regenerative capacity differs markedly, based on cellular and molecular components and evolutionary ideas. Here, we discuss several reasons for differences in regenerative capacity, including the properties of stem cells, dedifferentiation and transdifferentiation potentials, expression of regeneration-associated genes, epigenetic regulators, and immune responses. Comprehensive analyses of these perspectives would provide new insights into how to promote regeneration in mammals.