In this review, we describe three models of epidermis reconstructed on dermal substrates and utilized as an alternative to animal models. An almost normal epidermis is obtained when culture conditions are created that mimic the physiological conditions. The reconstruction of this epidermis allows us to evaluate the effects of substances such as retinoids and hormones on their target cell, namely the epidermal keratinocyte, and to vizualize the alteration of morphogenesis and architecture of the epidermis under the influence of such hormones. These cultures of reconstructed epidermis on firm substrates lifted to the air-liquid interface show a great potential in medical and pharmacological research since the systemic and topical actions of drugs as well as their metabolism can be studied.