Evidence from a randomized clinical trial showed that, in spite of the many surgical procedures effective in ameliorating the clinical appearance of photoaged skin, the only medical therapy with proven benefits in photoaged skin are topical retinoids, in particular tretinoin, isotretinoin, and tazarotene. The application of retinoids might not only clinically and biochemically repair photoaged skin, but their use might also prevent photoaging. Furthermore, new evidence suggests a beneficial role of topical retinoids in the treatment of intrinsically aged skin.