Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, in producing cytokines and in providing co-stimulation to cells of the adaptive immune system. NK cells play important roles in viral infections, autoimmunity, pregnancy, cancer and bone marrow transplantation. This review highlights recent developments in the understanding of the role of human NK cells in health and disease.