Immunosenescence is a process that primarily affects the T cell compartment of the immune system, although age-associated immunological alterations have also been demonstrated in the NK cell phenotype and function. A significant expansion in the number of NK cells is found in aging. The NK cytotoxic capacity of total peripheral blood lymphocytes is also well preserved, not only in healthy elderly people but also in centenarians. However, NK cell killing of K562 is impaired when considered in a per-cell basis, and this defect is associated with defective signal transduction after activation more than a diminished conjugate formation or killing capacity. We have studied the phenotype of NK cells in elderly donors fulfilling the Senieur criteria. We have also studied the capacity of these cells to be activated by IL2 when different NK cell functions, other than cytotoxicity, are considered. Our results confirm the increased percentage of NK cells in the elderly due to the expansion of the CD56dim subset that also show an altered pattern of activation markers, whereas no differences were found in the CD56bright subset. The response of NK cells to IL2 was found to be impaired when proliferation, expression of CD69, and Ca2+ mobilization were considered, whereas TNF-alpha production was not significantly affected. These results suggest that human NK cells do not escape the aging process, although senescence have a differential effect on distinct NK cell biological functions, ranging from severe to negligible impairment, depending on the parameters considered.