Natural Killer cells (NK) are part of the innate immunity, the first line of defence against several pathogens and cancer. Epigenetics regulates both NK functions and vulnerability of cancer cells to immune clearance. The job of researchers is to “play” with the epigenetic switches, in order to make the scales always tip in favour of tumour eradication. There is in fact an increasing interest in combining NK-based immunotherapies with epigenetic modulators, in order to improve their efficacy.