There is growing evidence for a role for epigenetic mechanisms in the development of autoimmune diseases. In most cases ofautoimmune disease the precise epigenetic mechanism involved remains to be resolved, however DNA hypomethylation accompanied by hypoacetylation ofhistone H3/H4 is commonly observed. Due to the reversible nature of epigenetic marks their maintenance enzymes such as DNA methyltransferases (DNMTs), histone deacetylases (HDACs) and histone lysine methyltransferases (HKMT) are attractive drug targets. Small molecule inhibitors of histone modification and DNA methylation maintenance are increasingly becoming available and will be useful chemical biological tools to dissect epigenetic mechanisms in these diseases. However, although epigenetic therapies used in cancer treatment are a promising starting point for the exploration of autoimmune disease treatment, there is a requirement for more specific and less toxic agents for these chronic diseases or for use as chemopreventative agents.