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Understanding how important phenotypic, developmental, and genomic features of animals originated and evolved is essential for many fields of biological research, but such understanding depends on robust hypotheses about the phylogenetic interrelationships of the higher taxa to which the studied species belong. Molecular approaches to phylogenetics have proven able to revolutionize our knowledge of organismal evolution. However, with respect to the deepest splits in the metazoan Tree of Life—the relationships between Bilateria and the four non-bilaterian phyla (Porifera, Placozoa, Ctenophora, and Cnidaria)—no consensus has been reached yet, since a number of different, often contradictory, hypotheses with sometimes spectacular implications have been proposed in recent years. Here, we review the recent literature on the topic and contrast it with more classical perceptions based on analyses of …