Skin is the largest human body organ that provides a major interface between the environment and the body and is constantly exposed to radiation from sun or artificial light sources. Such radiation may show different spectra ranging from ultraviolet to the infrared, which penetrate the skin and depending on the wavelength it reaches different parts of the skin. The skin contains a series of molecules (photosensitizers) that can absorb the radiation energy and generate 1O2 via energy transfer from the photosensitizer to molecular oxygen. Photosensitizers in skin can be assigned to endogenous compounds like endogenous porphyrins, vitamins or fatty acids or to exogenous compounds like medical drugs (e.g. antibiotics). The generation of 1O2 upon irradiation is frequently involved in many processes that affect the integrity of skin cells of the epidermis and dermis. Once produced in skin, 1O2 triggers cellular reactions, e.g. activation of transcription factors, interleukins, heme-oxygenase or matrix metalloproteinases. Depending on its concentration, 1O2 can cause apoptosis or necrosis in skin cells. In conclusion, 1O2 is a highly reactive and important molecule that comprises two contradictory effects in skin. On the one hand, the unintentional production of 1O2 by ambient radiation and endogenous photosensitizers harm skin cells yielding skin diseases. On the other hand, the therapeutic production of 1O2 can cure skin diseases.