This chapter focuses on new insights into the development of neural crest (NC) derivatives. NC is a highly pluripotent structure, the constitutive cells of which while exhibiting a striking migratory behavior spread over an embryo and settle in certain selected areas where they differentiate into a large variety of cell types. By means of the quail or chick-exchange system of definite regions of the neural primordium, prior to the onset of crest-cell migration, a fate map of the NC was constructed. The basic experimental paradigm was to exchange defined territories in an isotopic and isochronic manner between the embryos of two species. The cephalic NC gives rise to a large array of peripheral ganglia. In addition to melanocytes and endocrine cells, the cephalic crest also yields the mesectoderm from which a large majority of the head skeleton originates. The common precursors for glia and neurons are abundant in the NC. The in vitro clonal technique revealed that the cells with the potentiality to give rise to neurons, glia, melanocytes, and ectomesenchyme exist in the migratory cephalic NC, thus showing that the neural, melanocytic, and mesenchymal lineages are not completely segregated at the time of crest-cell dispersion. © 1992, Academic Press Inc.