Eccrine sweat glands, which are distributed over the whole bodies of primates and humans, have long been regarded mainly to have a function in thermoregulation. However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. In the meantime, a number of studies proved the importance of dermcidin in skin host defense. Several reports also state that peptides processed from the dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. This review summarizes the evidence gathered until now concerning the expression of dermcidin and the functional relevance of dermcidin-derived peptides.