Natural killer (NK) cells have been recognized as effector cells responsible for the elimination of blood-borne metastases. Newer evidence suggests that NK cells play an important role in the control of solid tissue metastases. NK cells have the ability to kill a broad variety of fresh or cultured “NK-resistant” tumor cell targets by mechanisms that are not dependent on perforin or granzyme secretion. Also, a subset of interleukin 2 (IL-2)-activated NK cells, which are called A-NK cells, is capable of extravasation, movement in solid tissues, localization to the sites of metastases, and killing tumor cellsin situ.Studies in experimental animals and in cancer patients indicate that systemic adoptive immunotherapy with A-NK cells and IL-2 is a tolerable and promising treatment for advanced solid tissue as well as hematologic neoplasms. In this article, antitumor functions of A-NK cellsin vitroandin vivoare reviewed, and the mechanisms responsible for their antitumor effects are considered.