Natural Killer (NK) cells are not just cytotoxic effectors of the innate immune response against tumors and infections but also important immunoregulators. They are activated by an intricate balance between signals provided by their inhibitory and activating receptors. Leptin, one major metabolic factor produced by adipocytes, appears to be strongly involved in obesity-induced dysimmunity and carcinogenesis. This paper reviews the studies investigating the effect of leptin on NK cells. Leptin, at level similar to that found in obesity, stimulate, in vitro, both the NK cell metabolic and lytic activities. In contrast, no significant association was observed, in vivo, between serum leptin and NK cytotoxicity whatever the model, diet-induced or constitutive obesity. These findings may be related to leptin resistance. (C) 2014 Elsevier Masson SAS. All rights reserved.