Epigenetic drug discovery has expanded significantly beyond histone deactylases (HDAC) in the past decade. This review covers significant new advances in the field across three more targets classes: bromodomains (BRD), arginine/lysine methyltransferases (RMT/KMT), and lysine demethylases (KDM). In each target section, a broad overview from a medicinal chemistry perspective is presented covering high-quality chemical biology tools being used to further expand the innate role of each target in cancer biology and in some examples facilitating preclinical target validation. In each target space, the review will also cover candidates currently in clinical investigation.