Pancreatic development is a complex and highly coordinated process in which two distinct histological and functional tissues (the exocrine and endocrine cell compartments) must arise from a common cell progenitor within a simple epithelium. The morphological events, the specification and differentiation of the different cell types (ductal, centro-acinar, acinar and endocrine) are under the control of a transcriptional factor network which needs to be tightly regulated in order to ensure timely and precise activation of the alternative gene expression programs that lead to formation of the different pancreatic lineages. Among the transcription factors involved in this regulatory cascade are members of the bHLH (basic helix-loop-helix) family, which play relevant roles during multiple processes of organogenesis. In this review we summarize the current knowledge on a specific set of pancreatic bHLH factors that regulate early pancreatic specification and later, initiate the differentiation program of the endocrine and exocrine cell types by governing cell fate decisions. The information about how these bHLH regulators dictate commitment to a pancreatic fate and modulate lineage choices should be valuable to manipulate both in vitro  and in vivo the plasticity of adult cells or the ability of pluripotent stem cells to acquire specific phenotypes. Ultimately, this knowledge will help to improve cell replacement-based therapies aimed at targeting important and devastating diseases such as diabetes, pancreatitis or pancreatic adenocarcinoma.