Specific immunity via antigen-recognizing T cells and B cells is crucial for complete host defense against infectious agents and cancer. However, the nonspecific arm of the host defense system plays an important role. NK cells, first described as an ever-present immunosurveillance mechanism against tumor development, are also important in early defense against microbes. With each type of microbe, NK cells use a different tactic to arm the host against the offending agent. To tackle intracellular viruses inaccessible to antibodies, they appear to lyse virus-infected fibroblasts and epithelial cells prior to maturation of the virions for dissemination in the host. Intracellular bacteria are dealt with in much the same manner, except that the targets are infected monocytes. Lastly, with organisms that cannot be directly killed, NK cells produce cytokines that can recruit and activate neutrophils. All accumulating evidence thus points to NK cells as a unique type of nonspecific lymphocytes that may be critical in either defense against microbes, particularly of the opportunistic nature, and in surveillance against certain types of tumors.