During vertebrate embryonic development, tissue patterning and differentiation are regulated by members of multigene families. Evolutionary expansion of these families is thought to have played a role in the evolution of anatomical complexity, including the origins of new cell and tissue types. A defining feature of vertebrates is an endoskeleton, the primary components of which are cartilage and bone. The molecular control of skeletal patterning has been the subject of intensive investigation for over two decades. More recently, comparative studies of organisms at key phylogenetic positions have highlighted the importance of gene duplication in the evolutionary diversification of connective tissues. Understanding the natural histories of gene families involved in skeletogenesis is therefore central to the issue of vertebrate skeletal evolution.