Epithelial ovarian cancer is the leading cause of death from gynecological cancers, largely owing to the development of recurrent intractable disease. Only a small number of distinct genetic mutations are known to contribute to ovarian carcinogenesis. Furthermore, understanding mechanistic genotype-phenotype links is complicated by frequent aneuploidy. Epigenetic deregulation is even more prominent, and ovarian cancers are replete with such aberrations that repress tumor suppressors and activate proto-oncogenes. Epigenetic therapies are emerging as promising agents for resensitizing platinum-resistant ovarian cancers. These drugs may also have the potential to alter epigenetic programming in cancer progenitor cells and provide a strategy for improving therapy of ovarian cancer.