UV irradiation may cause both beneficial and damaging effects, which depend on wavelength, radiant exposure, and UV sources. In this review, the potential beneficial effects of judicious UV exposure to augment wound healing, restoration of skin homeostasis, and selectively inactivate microorganisms over the host cells were briefly summarized. UVC should be investigated as an alternative approach for prophylaxis and treatment of localized infectious diseases, especially those caused by antibiotic-resistant pathogens. As a result, more extensive in vivo and clinical studies need to be carried out to investigate and optimize antimicrobial UVC treatment. Further study of cellular signaling that occurs after low doses of UVA exposure of tissue will allow the benefits as antioxidant, anti-inflammatory as well as wound-healing effects to be better defined. Technologies that help reduce the side effects (e.g., enhanced repair of UV-induced DNA damage to human cells, selective protection of human tissue, and cells from UV irradiation) of UV treatment are also worthy of being further investigated. New high-efficient light delivery technologies, for example, optical fibers, and optical clearing techniques, should be investigated to improve the penetration of UV irradiation in human skin and tissue. With the development of novel high-technology UV sources, using an NB wavelength range or a mono wavelength, such as LED, lasers, and microwave-generated UV plasma for UV phototherapy, will become as efficient biomedical modalities for the treatment of different localized and systemic dermatological disorders.