Background: Compared with other vertebrate taxa, mammals possess a very limited capacity for appendage regeneration. The antlers of deer are an exception in that they are periodically lost and fully regenerated throughout the life of an individual. Objective: In this paper we compare certain aspects of antler regeneration with regenerative processes in other vertebrates. Methods: Review of the literature. Results: Recent studies suggest that antler regeneration is a stem cell-based process and that these stem cells are located in the pedicle periosteum. There is evidence that signaling pathways known to operate during appendage regeneration in other vertebrates are also activated during antler regeneration. There are, however, also differences between antlers and other systems of epimorphic regeneration. Thus, contrary to amphibian limb regeneration, signaling from the wound epidermis appears not to be of crucial importance for antler regeneration. Healing of the casting wound typically involves no or only minor scarring, making antlers interesting subjects for researchers attempting to reduce scar formation during wound healing in humans. The fact that despite their enormous growth rate the antlers of intact and castrated deer appear to be resistant to malignant transformation furthermore offers research opportunities for cancer biology. Conclusions: Studying antler renewal as an example of mammalian appendage regeneration may provide crucial information for regenerative medicine to achieve its ultimate goal of stimulating limb regeneration in humans. A deeper understanding of the developmental mechanisms involved in antler renewal can also be useful for controlling induced regeneration processes in mammals.