Exocrine pancreatic cell types comprise greater than 90% of parenchymal cell mass in the adult pancreas. However, the factors regulating differentiation of acinar and ductal epithelial cells remain incompletely characterized. Like pancreatic islet cells, acinar and ductal cells arise from pluripotent precursors within embryonic pancreatic epithelium. Recent studies have suggested that a common pool of pluripotent stem cells is responsible for generating both endocrine and exocrine cell types, and that specific signaling pathways regulate a critical balance between endocrine and exocrine lineage commitment.