The neural crest is a multipotent cell population that arise at the border of the neural plate and non-neural ectoderm. Studies conducted in a number of model organisms including chickens, frogs, zebrafish and mice have been instrumental in elucidating this molecular mechanisms underlying neural crest formation. Signaling molecules of the Wnt, BMP, and FGF families and their downstream effectors have been shown to mediate neural crest induction. Transcription factors including members of the Snail and SoxE gene families as well as FoxD3, c-Myc and others have been implicated in specification of the neural crest. These studies represent an important step in understanding the regulatory interactions involved in generating this complex and interesting cell type.