Ultraviolet (UV) solar radiation produces harmful effects on the skin including sunburn, local immunosuppression, skin photoaging, and cutaneous malignancies. Although application of sunscreens is the "gold standard" for protecting the skin from UV radiation, studies have shown that currently used sunscreens can cause adverse skin and systemic reactions, owing to their penetration into the viable cutaneous strata and to transdermal absorption. This paper presents new nonpermeating sunscreens (NPSUN) suitable for use in cosmetic and pharmaceutical products. The basic idea behind the design of the new photoprotectors was to immobilize UV-absorbing moieties in the Jojoba oil chemical backbone. The physicochemical characteristics of NPSUNs allow these derivatives to remain confined to the upper stratum corneum where the sunscreen molecule acts, with no further clearance to deeper dermal strata or systemic circulation. As an example, no permeation across the skin of methoxycinnamate-NPSUN was observed during 24-hour in vitro experiments, after topical application of either unformulated substances or of methoxycinnamate-NPSUNs formulated in oil-in-water cream, in water-in-oil cream, or in Jojoba oil. Another approach to increase the photoprotective effect against the UV radiation is targeting the delivery of alpha tocopherol into the deeper skin layers and across the cell membranes. This is necessary for optimal photoprotection and prevention of malignant processes. For this purpose, ethosomal vitamin E compositions were designed, characterized, and tested. Efficient intracellular and dermal accumulation of vitamin E from ethosomes was demonstrated. A good clinical strategy could be the use of NPSUNs during direct UV exposure followed by the application of alpha-tocopherol compositions after short- or long-term solar radiation.