Explaining the high variability of regenerative ability across metazoan taxa is one of the major challenges in modern biology. Although common and widespread, regeneration shows a heterogeneous distribution and most authors consider regeneration capacity to be an ancestral trait that has been restricted or completely lost over the course of metazoan evolution. Basal Metazoans show the highest capacity for regeneration. By contrast, this feature is highly variable within bilaterians, with many taxa limited in their capacity for regeneration or not regenerating at all. The causes of the loss and/or maintenance of regeneration remain poorly understood, with most explanations invoking adaptive mechanisms. In the present study Metazoan regeneration is discussed with reference to stem cell biology, tissue plasticity, evolution of tissue complexity, cell turnover and lifespan. The presence or absence of regenerative ability cannot be seen only as an adaptation to a particular environment but can also be a consequence of body plan and developmental constraints such as may arise from the evolution of an adaptive immune system.