Natural killer (NK) cells represent important early effector cells of the innate immune system. They can lyse virally infected and malignant cells without prior sensitization, making them important members of the first line of defense. In addition, they participate in the regulation of immune responses and hematopoiesis by producing various cytokines and chemokines. These different functional capacities can to some extent be assigned to distinct NK cell populations. In humans, CD56(dim) NK cells featuring strong cytotoxic capacity can be easily distinguished from CD56(bright) NK cells, which predominantly produce cytokines and exert only marginal cytotoxicity. Murine NK cells lack CD56 expression and no correlate marker enabling identification of functional subpopulations has been described. Here, we summarize and discuss human NK cell populations in greater detail in order to evaluate their regulatory capacity and to detect alternative and distinctive markers, e.g. CXCR3 and CD27, which are shared by both humans and mice.