The neural crest is a transient, multipotent population of cells that arises at the border of the developing nervous system. After closure of the neural tube, these cells undergo an epithelial-to-mesenchymal transition (EMT) to delaminate and migrate, often to distant locations in the embryo. Neural crest cells give rise to a diverse array of derivatives including neurons and glia of the peripheral nervous system, melanocytes, and bone and cartilage of the face. A gene regulatory network (GRN) controls the specification, delamination, migration, and differentiation of this fascinating cell type. With increasing technological advances, direct linkages within the neural crest GRN are being uncovered. The underlying circuitry is useful for understanding important topics such as reprogramming, evolution, and disease.