Recent years have brought a paradigm shift for the role of the essential trace element zinc in immunity. Although its function as a structural component of many enzymes has been known for decades, current experimental evidence points to an additional function of the concentration of free or loosely bound zinc ions as an intracellular signal. The activity of virtually all immune cells is modulated by zinc in vitro and in vivo. In this review, we discuss the interactions of zinc with major signaling pathways that regulate immune cell activity, and the implications of zinc deficiency or supplementation on zinc signaling as the molecular basis for an effect of zinc on immune cell function.