Stem cells are defined by their ability to both self-renew and give rise to multiple lineages in vivo and/or in vitro. As discussed in other chapters in this volume, the embryonic neural crest is a multipotent tissue that gives rise to a plethora of differentiated cell types in the adult organism and is unique to vertebrate embryos. From the point of view of stem cell biology, the neural crest is an ideal source for multipotent adult stem cells. Significant advances have been made in the past few years isolating neural crest stem cell lines that can be maintained in vitro and can give rise to many neural crest derivatives either in vitro or when placed back into the context of an embryo. The initial work identifying these stem cells was carried out with premigratory neural crest from the embryonic neural tube. Later, neural crest stem cells were isolated from postmigratory neural crest, presumably more restricted in developmental potential. More recently it has been demonstrated that neural crest stem cell progenitors persist in the adult in at least two differentiated tissues, the enteric nervous system of the gut and the whisker follicles of the facial skin. In all cases, the properties of the stem cells derived reflect their tissue of origin and the potential of the progenitors becomes more restricted with age. In this chapter we will review this work and speculate on future possibilities with respect to combining our knowledge of neural crest gene function in the embryo and the manipulation of adult neural crest stem cells in vitro and eventually in vivo.