Exposures to ultraviolet radiation (UVR) during accidental or voluntary sun exposure or treatment with phototherapy or photochemotherapy have a significant impact on the skin. Many skin diseases such as psoriasis, atopic dermatitis, or cutaneous T-cell lymphoma significantly improve by photo(chemo)therapy, though the mechanisms behind the therapeutic effects of photo(chemo)therapy are still far from understood. Various pathways and means through which the energy of UVR from natural or artificial sources is ultimately transformed into biologic effects within the skin have been suggested and cutaneous sensory nerves, neuropeptides, neurotrophins, and certain nerve-related receptors have been among them. In fact a three-dimensional network of sensory nerve fibers derived from dorsal root ganglia intersperses all layers of the skin including the epidermis. In this forefront of defense against environmental impacts (including UVR) on the skin, sensory nerve fibers become targets by itself and closely contact resident and infiltrating cutaneous cells. Thus, terminals of cutaneous sensory nerve fibers, and neuropeptides within these fibers, are in a central position to participate in mediating therapeutic effects of photo(chemo)therapy.