Recent advances in the treatment of malignant haemopathies enable increased remission and cure rates, however, many patients relapse and finally die. Although specific immunity mediated by cytolytic T-lymphocytes might have an anti-cancer role, tumours escape from T-cell-based immune surveillance using various mechanisms, such as downregulation, mutation or loss of HLA class I molecules. As a consequence, these transformed cells could become targets for natural killer (NK) cells, whose cytotoxic capabilities are not blocked by HLA class I molecule engagement by specific inhibitory receptors. Novel developments in NK-cell research, particularly the identification of the role of non-HLA-restricted activating receptors (and in some cases of their ligands), have recently enabled us to reconsider NK-cell interactions with haematological malignant cells.