Irritant and allergic contact dermatitis are common inflammatory skin diseases induced by repeated skin contact with low molecular weight chemicals, called xenobiotics or haptens. Although both diseases may have similar clinical presentations, they can be differentiated on pathophysiological grounds. Irritant contact dermatitis (ICD) is a non-specific inflammatory dermatitis brought about by activation of the innate immune system by the pro-inflammatory properties of chemicals. Allergic contact dermatitis (ACD) corresponds to a delayed-type hypersensitivity response with a skin inflammation mediated by hapten-specific T cells. Recent progress in the pathophysiology of chemical-induced skin inflammation has shown that ICD and ACD are closely associated and that the best way to prevent ACD is to develop strategies to avoid ICD. The immunological diagnosis of ICD or ACD requires investigation of the presence (ACD) or absence (ICD) of antigen-specific T cells. The detection of T cells can be performed in the skin (collected from ACD lesions or positive patch tests) and/or in the blood, particularly by using the enzyme-linked immunospot assay (ELISPOT). This method, recently developed in ACD to metals, offers a new biological tool enabling the immunobiological diagnosis of ACD.