Natural killer (NK) cells comprise an important immune effector population that has been implicated in surveillance against tumor metastases and virally infected host cells, suppression of the humoral immune response, and regulation of hematopoiesis. These diverse functions require an initial cognate interaction between the NK effector cell and the target cell of interest. This specific interaction triggers the secretion of NK factors (i.e., lymphokines, cytolytic substances) which mediate NK activity. The target structures (TS) that stimulate the NK response remain ill-defined. While apparent TS heterogeneity may contribute to the difficulty in isolating distinct NK-TS, the proposed multifactorial nature of the NK cell-target cell interaction may represent the major complexity in the search for specific TS. Adhesion molecules such as ICAM-1 and LFA-3 may strengthen, while MHC antigens may weaken, the NK cell-target cell interaction. The following article analyzes the molecular interactions currently held to be relevant in target cell recognition by NK cells.