In addition to the function as a physical barrier human skin has been shown to be an important immune organ displaying various defense mechanisms, which can be divided into three major functional compartiments: (i) Epithelial defense, which is characterized by antimicrobial peptides and proteins (AP) and which can be induced in inflammatory lesions but also in the absence of inflammation. (ii) Innate-inflammatory immunity, which involves recognition of microbial compounds by particular receptors like Toll-like receptors (TLR) and subsequent activation of signalling pathways resulting in expression of pro-inflammatory cytokines and interferons, as well as genes of adaptive immunity. Interferon α (IFNα) produced by plasmacytoid dendritic cells (DC) may stimulate myeloid DC to produce IL-12 resulting in classical T-cell activation or to produce IL-23 activating IL-17 producing T-cells (IL-23/IL-17 pathway). (iii) Adaptive immunity, which is based on antigen presenting cells, T-cells and B-cells and which is characterized by specificity and memory. In contrast to epithelial defense and innate-inflammatory immunity, adaptive immune functions provide slowly reacting protection. Recent improvements of our knowledge of dysregulated immune pathways associated with inflammatory skin diseases represent an important basis of novel immunomodulatory treatment modalities.