Skin exposure to chemicals, natural or synthetic, may result in toxic reactions ranging from mild irritation to cutaneous allergy. These inflammatory reactions, subsequent to chemical exposure, derive from very different biological mechanisms. For a chemical to be a sensitizer, it must have the ability to bind to protein so that a nonself antigen can be produced. The evidence indicates that normally this binding occurs by covalent bond formation. From a chemical point of view, chemical sensitizers can be divided into three categories: Haptens that can react directly with nucleophilic side chains of aminoacids. Prohaptens that need an enzymatic transformation to become reactive haptens. Prehaptens that need a nonenzymatic chemical transformation such as air oxidation to become reactive haptens. Molecular mechanisms associated with irritant contact dermatitis are more difficult to investigate and demonstrate as they are very often based on reversible interactions with biological systems. However, one can mention acido-basic, surfactant, and alkylating properties.