During embryonic development, the skin, the largest organ of the human body, and nervous system are both derived from the neuroectoderm. Consequently, several key factors and mechanisms that influence and control central or peripheral nervous system activities are also present and hence involved in various regulatory mechanisms of the skin. Apparently, this is the case for the ion and non-ion selective channels as well. Therefore, in this review, we shall focus on delineating the regulatory roles of the channels in skin physiology and pathophysiology. First, we introduce key cutaneous functions and major characteristics of the channels in question. Then, we systematically detail the involvement of a multitude of channels in such skin processes (e.g. skin barrier formation, maintenance, and repair, immune mechanisms, exocrine secretion) which are mostly defined by cutaneous non-neuronal cell populations. Finally, we close by summarizing data suggesting that selected channels are also involved in skin diseases such as e.g. atopic dermatitis, psoriasis, non-melanoma cancers and malignant melanoma, genetic and autoimmune diseases, etc., as well as in skin ageing.