The annual regrowth of deer antlers is a unique case of extensive appendage regeneration in mammals. This review compares basic aspects of antler regeneration with epimorphic regeneration in other vertebrate taxa. The mesenchymal cells that build up the regenerating antler are not derived from dedifferentiated cells in the pedicle stump, but from the proliferation of cells of the pedicle periosteum; and based on different lines of evidence it has more recently been suggested that the pedicle periosteum contains stem cells that are periodically activated to produce a new antler. This constitutes a difference to urodele limb regeneration, where the blastema is (largely) formed from dedifferentiated cells. Antler regeneration involves healing of the large casting wound with no or only minor scarring, making the antler an interesting model for the control of scarring in mammals. Contrary to urodele limb regeneration, antler regrowth does not depend on a functional nerve supply. In our view, a comparative analysis of different regeneration phenomena, including antler regeneration, probably offers the best chance for achieving significant progress in regenerative medicine.