Natural-killer (NK) cells form a first line of defence against pathogens or host cells that are stressed and/or cancerous. NK cells express surface receptors that receive signals from the environment and determine their response to foreign or malignant cells. NK cells respond to these signals by producing effector molecules that can both directly suppress tumour growth and convey important information to the rest of the immune system. We have only recently begun to appreciate the potential for NK cells to be rationally manipulated in the treatment of human cancers.