Natural killer (NK) cells are cytotoxic cells that play a critical role in the innate immune response against infections and tumors. Recent studies on NK cell biology have demonstrated that besides their cytotoxic function, NK cells express cytokine and chemokine receptors and also that they secrete other immunoregulatory cytokines and chemokines, supporting their relevance in the regulation of the immune response by promoting downstream adaptive, Th1 mediated, responses against infections. Immunosenescence is the deterioration of the immune response associated with aging. It is characterized mainly by a defective T cell response, but includes changes in the number and function of other cells of the innate immune system. Age-associated alterations in the number and function of NK cells have been reported. There is a general consensus that a progressive increase in the percentage of NK cells with a mature phenotype occurs in elderly donors associated with an impairment of their cytotoxic capacity when considered on a “per cell” basis. The response of NK cells from elderly individuals to IL-2 or other cytokines is also decreased in terms of proliferation, expression of CD69 and killing of NK-resistant cell lines. Furthermore early IFN-γ and chemokine production in response to IL-2 or IL-12 is also decreased. However aging does not significantly alter other NK cell functions such as TNF-α production or perforin induction in response to IL-2. The percentage of T cells that co-express NK cell markers is also increased in aging. These results indicate that the increase in the number of “classical” mature NK and NK/T cells in aging is associated with a defective functional capacity of NK cells. Low NK cell number or function in elderly individuals is associated with increased mortality risk and increased incidence of severe infections, supporting the role of NK cells in the defense against infections in the elderly.