Natural killer (NK) cells represent a distinct lymphoid population characterized by unique phenotypic and functional features. NK cells were originally identified on a functional basis as this denomination was assigned to lymphoid cells capable of lysing tumor cell lines in the absence of prior stimulation in vivo or in vitro. Both their origin and the mechanism(s) mediating their function remained mysterious until recently. Regarding their origin, it has been shown that NK cells derive from a precursor common to T cells and expressing the CD34+CD7+ phenotype. In addition, functional NK cells can be obtained in vitro and in vivo from (CD34+) haematopoietic precursors isolated from several different sources. The cell maturation in vitro has been shown to require appropriate feeder cells and/or IL-15. The molecular mechanisms underlying the ability of NK cells to discriminate between normal and tumor cells, predicted by the “missing self hypothesis”. have been clarified only during the past decade. It has been shown that NK cells recognize MHC-class I molecules through surface receptors delivering inhibitory, rather than activating, signals. Accordingly, NK cells lyse target cells that have lost (or express low amounts of) MHC class I molecules. This event occurs frequently in tumors or in cells infected by some viruses such as certain herpesviruses or adenoviruses. In addition to providing a first line of defence against viruses, NK cells release various cytokines and chemokines.