Photodamage of the skin can be a detriment to physical and psychological health with a consequent negative impact on both personal and professional life. Medical treatments for photodamaged skin include topical all-trans-retinoic acid (tretinoin) as well as moisturizers, chemical peels, dermabrasion, α hydroxy acids and cosmetic surgery. Of these treatment options, only tretinoin has been subjected to large-scale, controlled studies to substantiate its clinical efficacy and long-term benefits. This review summarizes the use of various therapies and presents available clinical and histologic results of systematic trials, including the few studies of retinoid compounds other than tretinoin. Among the extensive data on topical tretinoin are long-term treatment results that provide evidence of ultrastructural changes. These histologic findings suggest that fundamental cellular effects may be responsible for the clinical benefits, which are sustained even when treatment frequency is reduced. It thus appears that tretinoin therapy at least partially restores photodamaged skin to the predamaged state.