Epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNA expression, contribute to regulate islet cell development and function. Indeed, epigenetic mechanisms were recently shown to be involved in the control of endocrine cell fate decision, islet differentiation, β-cell identity, proliferation, and mature function. Epigenetic mechanisms can also contribute to the pathogenesis of complex diseases. Emerging knowledge regarding epigenetic mechanisms suggest that they may be involved in β-cell dysfunction and pathogenesis of diabetes. Epigenetic mechanisms could predispose to the diabetic phenotype such as decline of β-cell proliferation ability and β-cell failure, and account for complications associated with diabetes. Better understanding of epigenetic landscapes of islet differentiation and function may be useful to improve β-cell differentiation protocols and discover novel therapeutic targets for prevention and treatment of diabetes.