An outstanding problem in vertebrate paleobiology is the origin of vertebrates, which has been an issue for well over a hundred years. How are vertebrates related to invertebrates; what characteristics are specific to vertebrates in terms of their body plan; and what genetic innovations were necessary in order to develop these vertebrate-specific features remain questions. Answers are not likely to be found in the fossil record of early vertebrates, but require tools that have come into use only recently.