In the innate immune Natural killer (NK) cellssystem, natural killer (NK) cells represent a Epigenetichighly important subset of cells with utmost importance in the control of transformed cell and tumor inflammation. Functionally, NK cells are highly potent producers of IFN-γ and release granzymes during degranulation, which play a significant role in the control of cancerous or virus-infected cells. Identification of key factors to improve the ability of NK cells to fight infections and cancer is detrimental to improve NK cell-based immunotherapies. Based on recent findings in the field of epigenetics in the immune system, epigenetic modifiers are deemed to be a “New Hope” to improve the immune response against infections and cancerous cells. Over the last decade, we gained significant evidence that epigenetic regulation plays an important part in NK cell development and function. We here describe the relatively recent interest in the role of epigenetic modifiers for NK cell development and function, which provides copious but challenging possibilities to improve NK cell-based immunotherapies in cancer, autoimmune disorders, and infectious diseases.