The neural crest is a transient structure in vertebrate embryos that produces migratory cells with an astonishing developmental potential. While neural crest fate maps have originally been established through interspecies transplantation assays, dye labeling, and retroviral infection, more recent methods rely on approaches involving transgenesis and genome editing. These technologies allowed the identification of minor neural crest-derived cell populations in tissues of non-neural crest origin. Furthermore, in vivo multipotency at the single cell level and stage-dependent fate acquisitions were demonstrated using genetic technologies. Finally, recent reports indicate that neural crest-derived cells become activated in response to injury to secrete factors supporting tissue repair. Thus, neural crest-derived cells apparently contribute to tissue formation and regeneration by cell autonomous and non-autonomous mechanisms.