The axial skeleton in all vertebrates is composed of similar components that extend from anterior to posterior along the body axis: the occipital skull bones and cervical, thoracic, lumbar, sacral, and caudal vertebrae. Despite significant changes in the number and size of these elements during evolution, the basic character of these anatomical elements, as well as the order in which they appear in vertebrate skeletons, have remained remarkably similar. Through extensive expression analyses, classic morphological perturbation experiments in chicken and targeted loss-of-function analyses in mice, Hox genes have proven to be critical regulators in the establishment of axial skeleton morphology. The convergence of these studies to date allows an emerging understanding of Hox gene function in patterning the vertebrate axial skeleton. This review summarizes genetic and embryologic findings regarding the role of Hox genes in establishing axial morphology and how these combined results impact our current understanding of the vertebrate Hox code. Developmental Dynamics 236:2454–2463, 2007. © 2007 Wiley-Liss, Inc.