Abstract The neural crest is a transitory tissue of the vertebrate embryo that originates in the neural folds, populates the embryo, and gives rise to many different cell types and tissues of the adult organism. When neural crest cells initate their migration, a large fraction of them are still pluripotent, that is, capable of generating progeny that consists of two or more distinct phenotypes. To elucidate the cellular and molecular mechanisms by which neural crest cells become committed to a particular lineage is therefore crucial to the understanding of neural crest development and represents a major challenge in current neural crest research. This chapter discusses selected aspects of neural crest cell differentiation into components of the peripheral nervous system. Topics include sympathetic neurons, the adrenal medulla, primary sensory neurons of the spinal ganglia, some of their mechanoreceptive and proprioceptive end organs, and the enteric nervous system.