Immune checkpoint blockade (ICB) increases the activity of tumor-resident cytotoxic lymphocytes and has revolutionized cancer treatment. Current class-leading therapies block inhibitory pathways in tumor-infiltrating CD8+ T cells, but recent studies have deciphered similar programs in natural killer (NK) cells. NK cells are critical for tumor immune surveillance, particularly for the control of metastatic cells or hematological cancers, although how NK cells specifically recognize tumors, the dominant negative feedback pathways and ultimately how tumors escape NK cell control remains to be defined. Intra-tumour NK cell frequency is prognostic of cancer survival and predicts ICB response with NK cells emerging as a catalyst for tumor inflammation. This presentation will summarise recent advances that have illuminated inhibitory checkpoints in NK cells and outlines emerging approaches to unleash the potential of NK cells in immunotherapy.