Human Merkel cells were first described by Friedrich S. Merkel in 1875 and named “Tastzellen” (touch cells) assuming a sensory touch function within the skin. Only ultrastructural research revealed their characteristics such as dense-core granules, plasma membrane spines and dendrites as well as a loosely arranged cytoskeleton. Biochemical analysis identified the expression of very specific cytokeratins (most notably CK 20) allowing the immunohistochemical detection of Merkel cells. In humans, they occur within the basal epidermis, being concentrated in eccrine glandular ridges of glabrous skin and in Haarscheiben of hairy skin, within belt-like clusters of hair follicles, and in certain mucosal tissues. Within the human skin, the dense-core granules contain heterogeneously distributed neuropeptides, some of which might work as neurotransmitters through which Merkel cells and their associated nerves exert their classical function as slowly adapting mechanoreceptors type I. This is the case in the Haarscheiben, small sensory organs containing keratinocytes with a special program of differentiation that includes the expression of CK 17 and Ber-EP4. Other peptides may act as growth factors and thus might participate in growth, differentiation and homeostasis of cutaneous structures. It is not yet clear whether the Merkel cell carcinomas, aggressive skin carcinomas, indeed arise from Merkel cells. We summarize and discuss data on the distribution, function and heterogeneity of human Merkel cells in normal and diseased skin.