Numerous physiological processes in the human skin are mediated by nitric oxide, a gaseous signalling molecule. Almost every type of skin cell may produce nitric oxide, it is possible to generate nitric oxide without the need of enzymes. Nitric oxide plays a crucial role in regulating apoptosis, keratinocyte differentiation and proliferation, the protective properties of the epidermal barrier, and the structure and functions of the microcirculatory bed. Nitric oxide is involved in immunological and inflammatory responses, hair growth regulation, and wound healing processes. It mediates ultraviolet-induced processes such as erythema and edema development and participates in melanogenesis. Furthermore, the ability of nitric oxide to bind reactive oxygen species and prevent lipid peroxidation gives it antioxidant qualities. This coordinated action of nitric oxide on gene expression and membrane integrity effectively protects cells from ultraviolet A-induced apoptosis and necrosis. Furthermore, nitric oxide can be considered as a molecule that inhibits the development of cancer and photoaging. It directly harms microorganisms and indirectly activates the immune system, exhibiting antibacterial, antiviral, and antifungal qualities. Notably, nitric oxide is effective against antibiotics-resistant bacteria. All of the aforementioned findings suggest that nitric oxide is a gaseous mediator that can protect skin function. © 2025 Elsevier B.V., All rights reserved.