Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56^bright CD16^dim/− and CD56^dim CD16⁺, respectively. In this review, we will focus on the CD56^bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56^dim NK cells. CD56^bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.