The field of epigenetics broadly seeks to define heritable phenotypic modifications that occur within cells without changes to the underlying DNA sequence. These modifications allow for precise control and specificity of function between cell types-ultimately creating complex organ systems that all contain the same DNA but only have access to the genes and sequences necessary for their cell-type-specific functions. The pancreas is an organ that contains varied cellular compartments with functions ranging from highly regulated glucose-stimulated insulin secretion in the β-cell to the pancreatic ductal cells that form a tight epithelial lining for the delivery of digestive enzymes. With diabetes cases on the rise worldwide, understanding the epigenetic mechanisms driving β-cell identity, function, and even disease is particularly valuable. In this chapter, we will discuss the known epigenetic modifications in pancreatic islet cells, how they are deposited, and the environmental and metabolic contributions to epigenetic mechanisms. We will also explore how a deeper understanding of epigenetic effectors can be used as a tool for diabetes therapeutic strategies.