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Publisher Summary The human skin is the largest organ of the body that provides a protective barrier to ensure that exogenous noxious agents do not affect the homeostasis of the organism. Knowledge of skin immunological defense mechanisms is advancing rapidly and provides new insights into the normal homeostasis of this vital organ, improving the understanding of various disease processes. Structure–function correlations are being expanded to include detailed molecular dissection of the events that are principally responsible for the skin immune system (SIS), and which guide the coordinated intercellular interplay crucial for immune surveillance involving the skin. For the understanding of cutaneous immunology, it is essential to keep in mind what distinguishes the skin from other organs. From such a platform of specific immunophysiology of the skin its dysregulations as it knows them in the form of a surprisingly large number of inflammatory and immunodermatological diseases can be understood.