The specialized endocrine and exocrine cells of the pancreas originally derive from a pool of apparently identical cells in the early gut endoderm. Serial changes in their gene expression program, controlled by a hierarchy of pancreatic transcription factors, direct this progression from multipotent progenitor cell to mature pancreatic cell. When the cells differentiate, this hierarchy of factors coalesces into a network of factors that maintain the differentiated phenotype of the cells. As we develop an understanding of the pancreatic transcription factors, we are also acquiring the tools with which we can ultimately control pancreatic cell differentiation.