There has been a tremendous interest to understand the mechanisms that regulate gene expression in autoimmunity and their effect on disease phenotypes by exploring different epigenetic mechanisms. In this review, we will introduce lupus epigenetics through reviewing historical key findings, then we will focus on the most recent and relevant findings in this field reflecting our own and naturally biased opinion. In addition to uncovering more methylation-sensitive loci in critical genes and proposing a role for these genes in the pathogenesis of lupus, there has been a great interest in high-resolution unbiased genome-wide epigenetic studies to investigate aberrant methylation and histone code patterns, the two major epigenetic markers. In recent years, we have also witnessed an increasing interest in the role of microRNAs in the pathogenesis of lupus, and as candidate molecules with intriguing therapeutic potentials. Epigenetics is an exciting field that is serving as a link, as we currently understand, between genetic susceptibility and the environment in predisposing to lupus. Certainly, epigenetic aberrancies play a fundamental role in propagation of the lupus phenotype. Whether the available epigenetic-modifying agents would be useful treating human lupus is still an open question, but is unlikely in our opinion. Indeed, gene-specific epigenetic modifiers will be a challenging and an exciting area for future research.