Zinc is an essential trace element for humans and plays a critical role both as a structural component of proteins and as a cofactor in about 300 enzymes. Zinc deficiency was, for example, reported to affect the immune response and the endocrine system and to induce and modify brain disorders. Besides hereditary zinc deficiency, zinc deficiency – at least in mild forms – is nowadays a very abundant health issue. Today, an estimated 20% of the population worldwide is at risk of developing zinc deficiency with a high number also in industrialized countries. The major risk factors to develop zinc deficiency in industrialized nations are aging and pregnancy. Mechanistic and behavioral studies on the effects of zinc deficiency have mainly been performed using animal models. However, in combination with the few studies on human subjects, a picture emerges that shows importance of adequate nutritional zinc supply for many processes in the body. Especially the immune system and brain development and function seem to be highly sensitive to zinc deficiency. Here, we provide an overview on the effects of zinc deficiency on different organ systems, biological processes, and the associations of zinc deficiency with pathologies observed in humans and animal models.