Human Natural Killer Receptors and Their Ligands (Roberto Biassoni and Cristina Bottino, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Claudia Cantoni, Universita degli Studi di Genova, Istituto Giannina Gaslini, Genova, Italy; Alessandro Moretta, Universita degli Studi di Genova, Genova, Italy). Natural killer (NK) cells are a lymphocyte subpopulation that are important effectors of innate immune responses against infectious pathogens. They are thought to play an important role in host defense, not only against virally infected cells, but also in killing of tumor cells. Recent progress indicates that NK cells express an array of receptors, some of them clonally distributed, able to modulate the natural cytotoxicity. Three NK-specific activating receptors have been characterized; they belong to a novel receptor family called natural cytotoxicity receptors (NCR) and are represented by NKp46, NKp44, and NKp30. These receptors, upon engagement by their specific ligands, induce a strong activation of NK-mediated cytotoxic activity. This overview discusses the receptors (both activating and inhibitory) expressed by NK cells and their ligands. Finally, the dysfunction of one of these molecules occurring in a genetically inherited immunodeficiency is discussed.