Evidence has been reviewed which indicates that NK cells play a role in the control of metastasis dissemination. Both activation of endogenous NK cells in a tumor-bearing host and adoptive transfer of ex vivo activated NK cells may be therapeutically beneficial. The small number of phase I/II clinical trials of AIT with A-NK cells performed in patients with cancer so far does not allow firm conclusions, except to ascertain the feasibility and a lack of toxicity of this form of therapy. Although numerous trials have been performed with BRMs, many of which are known to upregulate NK activity in vivo, a general lack of correlations between clinical responses or survival and upregulated NK activity in the peripheral blood has dampened enthusiasm for biological therapies. However, these clinical trials have been confined largely to patients with advanced metastatic disease. It is highly likely that tumor-induced immunosuppression plays a crucial role in neutralizing the benefits of BRM therapy, and that levels of effector cell activation sufficient for metastasis elimination are seldom achieved in this clinical setting. On the other hand, administration of BRMs in the adjuvant setting could be more effective and when combined with monitoring for effector cell functions might perhaps provide a better guide for achieving the levels of endogenous NK activity necessary for elimination of remaining or occult metastases. An improved understanding of NK cell biology in cancer patients is likely to serve as a positive reinforcement for design of a new generation of clinical trials incorporating novel approaches to NK cell mediated cancer therapy.