SOX10 is a member of the high-mobility group-domain SOX family of transcription factors, which are ubiquitously found in the animal kingdom. Disruption of neural crest development in the Dominant megacolon (Dom) mice is associated with a Sox10 mutation. Mutations in human Sox10 gene have also been linked with the occurrence of neurocristopathies in the Waardenburg-Shah syndrome type IV (WS-IV), for which the Sox10(Dom) mice serve as a murine model. The neural crest disorders in the Sox10(Dom) mice and WS-IV patients consist of hypopigmentation, cochlear neurosensory deafness, and enteric aganglionosis. Consistent with these observations, a critical role for SOX10 in the proper differentiation of neural crest-derived melanocytes and glia has been demonstrated. Emerging data also show an important role for SOX10 in promoting the survival of neural crest precursor cells prior to lineage commitment. Several genes whose regulation is dependent on SOX10 function have been identified in the peripheral nervous system and in melanocytes, helping to begin the identification of the multiple pathways that appear to be modulated by SOX10 activity. In this review, we will discuss the biological relevance of these target genes to neural crest development and the properties of Sox10 as a transcription factor.