Natural killer cells (NK cells) are innate lymphoid cells that function as both cytotoxic effectors and regulators of immune responses. NK cells develop from common lymphoid progenitor cells primarily in the bone marrow and are educated to become self-tolerant by recognition of self MHC class I molecules. Mature NK cells migrate to the liver, uterus, thymus, and peripheral lymphoid organs where they give rise to tissue-specific, functionally distinct mature NK cell subsets. NK cells express a large number of receptors that deliver either activating or inhibitory signals, and the relative balance of these signals controls NK cell activity. NK cells are activated following the detection of abnormalities in target cells such as the loss of MHC class I expression or up-regulation of stress-induced ligands that occurs in response to infection or malignant transformation. Their activation triggers Perforin/Granzyme-induced target cell lysis and the production of a number of cytokines including IFN-gamma and TNF-alpha, which also allows NK cells to contribute to the activation of the adaptive immune response. Their ability to specifically attack and eliminate stressed cells, while maintaining tolerance to normal, healthy cells has led to the compelling suggestion that NK cells may have therapeutic potential as anti-cancer agents.