The development of the pancreas and determination of endocrine cell fate are controlled by a highly complex interplay of signaling events and transcriptional networks. It is now known that an interconnected epigenetic program is also required to drive these processes. Recent studies using genome-wide approaches have implicated epigenetic regulators, such as DNA and histone-modifying enzymes and non-coding RNAs, to play critical roles in pancreas development and the maintenance of cell identity and function. Furthermore, genome-wide analyses have implicated epigenetic changes as a casual factor in the pathogenesis of diabetes. In the future, genomic approaches to further our understanding of the role of epigenetics in endocrine cell development and function will be useful for devising strategies to produce or manipulate β-cells for therapies of diabetes.