The Episkin model consists of a reconstructed human epidermis grown on the surface of a cell-free bilayered human dermal substitute that can be used as an in vitro model for toxicological and pharmacological studies. On this model, different applications in the assessment of cosmetics safety and efficacy have been reviewed: cutaneous tolerability of topically applied products, phototoxicity evaluation of UV and/or chemical compounds, and the photoprotective action of sunscreens. The demonstration of a barrier function in the Episkin model and the existence of metabolizing activities toward xenobiotics is encouraging for its future pharmacological use. In addition to the avoidance of the use of animals, the Episkin model could be of great interest in the mechanistic studies of the effects of topically applied compounds.