Natural killer (NK) cells are anti-tumor and anti-viral effector cells. These cells show increased cytolytic activity upon stimulation with interleukin 2 or chemokines. In addition, members of the C, CC, CXC, or CX3C chemokines induce the in vitro chemotaxis of NK cells and contribute to their in vivo tissue accumulation. Chemokines induce various intracellular signaling pathways in NK cells by activating members of the heterotrimeric G-proteins. Understanding these pathways should provide an insight into NK cell activation, in vivo distribution, and tissue localization. Based on evidence showing the high lytic activity of these effector cells against transformed or virally infected cells, it is suggested that NK cells can be used to maximize the immunotherapeutic protocols for AIDS and cancer patients.