Underlying any analysis on the evolution of development is a phylogenetic framework, whether explicitly stated or implied. As such, differing views on phylogenetic relationships lead to variable interpretations of how developmental mechanisms have changed through time. Over the past decade, many long-standing hypotheses about animal evolution have been questioned causing substantial changes in the assumed phylogenetic framework underlying comparative developmental studies. Current hypotheses about early metazoan history suggest that three, not two, major lineages of bilateral animals originated in the Precambrian: the Deuterostomes (e.g., seastars, acorn worms, and vertebrates), the Ecdysozoans (e.g., nematodes and arthropods), and the Lophotrochozoans (e.g., annelids, mollusks, and lophophorates). Although information in Hox-genes bears directly on our understanding of early metazoan evolution and the formation of body plans, research effort has been focused primarily on two taxa, insects and vertebrates. By sampling a greater diversity of metazoan taxa and taking advantage of biotechnological advances in genomics, we will not only learn more about metazoan phylogeny, but will also gain valuable insight as to the key evolutionary forces that established and maintained metazoan bauplans.