Major advances in the molecular genetics, paleobiology, and the evolutionary developmental biology of vertebrate skeletogenesis have improved our understanding of the early evolution and development of the vertebrate skeleton. These studies have involved genetic analysis of model organisms, human genetics, comparative developmental studies of basal vertebrates and nonvertebrate chordates, and both cladistic and histological analyses of fossil vertebrates. Integration of these studies has led to renaissance in the area of skeletal development and evolution. Among the major findings that have emerged is the discovery of an unexpectedly deep origin of the gene network that regulates chondrogenesis. In this chapter, we discuss recent progress in each these areas and identify a number of questions that need to be addressed in order to fill key gaps in our knowledge of early skeletal evolution.