Abstract Skin serves as an effective, though imperfect protective barrier between the body and the environment. When exposed to a chemical, some of the chemical passes through the outer layer (stratum corneum) into the skin itself, where, depending on its potency, it may cause a number of local skin effects including irritant and allergic contact dermatitis, as well as skin cancers. Further, some of this material may also penetrate into the skin capillaries and into the systemic circulation, often constituting an important route of whole-body exposure for environmental chemicals. A number of approaches have been developed to estimate and predict the extent to which a chemical penetrates both into and through the skin, as well as it's potential for metabolism within the skin. These include experimental methods (in vivo animal studies and in vitro studies using skin and skin surrogates), as well as predictive mathematical modeling techniques. Such studies are also critical for understanding the mechanisms involved in both skin toxicity and dermal absorption and penetration.