The immune system is characterized by its dynamic responses to various infectious agents through different types and intensities of immune reactions. However, the immune system must also tolerate self and nonharmful environmental antigens. The immune system also exhibits memory for the primary infection, which enables efficient clearance of the same pathogen upon subsequent infections. One of the cellular machineries that deals with such complex demands on the immune system is epigenetics. Epigenetic modifications, which include different covalent modifications on histones and DNA, are characterized by their “multidimensional” regulation of gene activities. These epigenetic hallmarks not only mediate the switching on and off of transcription, but also regulate the kinetics and robustness, maintain the transcriptional status, and define the responsiveness or unresponsiveness of genes to external stimuli, thus elaborating the well-organized immune system. This chapter describes the epigenetic regulation of immune cell development, initially presenting the basic epigenetic regulatory mechanisms of gene activity and then presenting the epigenetic mechanisms that mediate the development of various immune cell types, with examples from both innate and adaptive arms of immunity.