Complex organs like the nervous system are composed of different cell types which are all derived from multipotent stem cells. In vertebrates, a transient population of stem cells, the neural crest, generates the entire peripheral nervous system as well as non-neural progeny. The developmental processes of cellular differentiation and proliferation require precise coordination and control. Errors in the programs that regulate stem cell function can lead to defects that manifest in developmental disorders, in some cases they might even induce cancer. It is therefore of fundamental interest to understand the mechanisms of stem cell maintenance and differentiation. Using the neural crest as a model system helps us not only to understand the role of stem cells in development but might also lead to new aspects for the cure of stem cell-related diseases.