Epigenetic mechanisms control the expression of both canonical coding genes and non-coding regulatory RNA species. Such mechanisms include DNA methylation changes at predominantly CpG sites in humans, modification of histone tails, packaging of DNA into nucleosomes, and control of nucleosome positioning or nucleosome remodelling. These steps ultimately impact upon gene expression and therefore cell state definition. It has been established that a variety of epigenetic aberrations seen in cancers can complement genetic abnormalities in tumorigenesis and some are almost certainly driving events for malignant potential. Epigenetic abnormalities are potentially reversible with respect to pharmacological intervention for cancer management. In this chapter we will discuss the evolution of epigenetic therapy over the last approximately 40 years, our current understanding of clinically available agents and future approaches towards drug development, regulatory studies and clinical efficacy assessment.