Several vertebrate species are able to epimorphically regenerate tissue of appendages or wholeappendages such as fingertips, limbs, fins, tails, antlers, and ear tissue via the formation of a blastemaof proliferating cells. For structure such as mammalian ear tissue and fingertips and antlers, the originof the cells for regeneration is uncertain, but in others, such as fish fin regeneration and amphibianlimb and tail regeneration, studies revealed that the blastema is formed by the dedifferentiation ofmature cells local to the region of injury. Moreover, regeneration requires specification of the identityof new tissues to be made either in lower or higher vertebrates. Whether this process relies only onintrinsic regulative properties of regenerating tissues or whether wound signaling provides input intotissue repatterning is not known. In this review, authors have made efforts to put emphasis onsignaling events, importance of polarity during regeneration and put forth how the limitations ofregeneration could be overcome in higher vertebrates such as animals and humans.