This chapter discusses some of the basic principles that have emerged from the study of neural crest biology. It discusses the origin of the neural crest in the embryo and considers some of the general principles underlying neural crest diversification. Finally, the chapter discusses what is known about how specific derivatives of the neural crest are generated. The neural crest has captured the imagination of developmental biologists for over a century. There are two principal reasons for this. First, it is a highly migratory cell population and very little is known about the mechanisms that precisely guide neural crest cells to specific sites in the embryo. Second, the neural crest gives rise to an enormous diversity of cell types, including the entire peripheral nervous system, melanocytes, endocrine cells, and much of the connective tissue, bone, and cartilage of the face and skull. Neural crest cells arise at the junction between the prospective epidermis and the prospective neural plate in all vertebrates, regardless of whether the neural crest ultimately migrates from the open neural folds, the closed neural tube, or an ectodermal thickening at the neural plate-epidermis boundary. Although a number of models have been proposed for how neural crest cells are generated, the weight of evidence at present suggests that neural crest arises from local cell-cell interactions between the epidermis and the neural plate. ; © 1999 Academic Press. We are very grateful to Dr. Clare Baker for her many helpful suggestions and comments on the manuscript, and for providing us with an invaluable list of references. A.K.G. is supported by NIH Grant RO3 DC03630-01. Work in our laboratory was supported by NIH Grants NS36585 and NS34671.