The axial skeleton in all vertebrates is comprised of similar structures that extend from anterior to posterior along the body axis: the occipital skull bones, cervical, thoracic, lumbar, sacral and caudal vertebrae. Despite significant changes in the number and size of these elements during vertebrate evolution, the basic character of these anatomical elements, as well as the order in which they appear, has remained strikingly similar. Extensive expression analysis, classic embryology experiments in chick and targeted loss-of-function mutant analyses in mice have clearly demonstrated that Hox genes are key regulators of morphology along the axial skeleton. The cumulative data from this work provides an emerging understanding of Hox gene function in patterning the vertebrate axial skeleton. This chapter summarizes genetic, molecular and embryologic findings on role of Hox genes in establishing axial morphology and how these combined results impact our current understanding of the 'Hox code'.