Why does regeneration occur? And why, when it manifests itself, does it do so in some but not all metazoan species? Hence, what are the permissive or inhibitory factors operating behind this phenomenon? When it comes to regeneration, many questions, such as these, remain unanswered. In fact, the problem of animal regeneration has withstood the probing of scientific inquiry for over 250 years and still awaits a satisfactory mechanistic explanation. In this essay, I will review the distribution and the modes of regeneration that are found in the different metazoan phyla. Also, I will re-examine ideas on its evolutionary origins, and discuss its possible relationship to both asexual reproduction and embryogenesis. This endeavor has two objectives. First, to bring forward an interpretation of regeneration which integrates evolutionary and developmental considerations into its discussion. And second, to suggest a comparative experimental approach to this problem that may bring us closer to understanding the molecular basis of this long-standing biological problem. BioEssays 22:578–590, 2000. © 2000 John Wiley & Sons, Inc.