Allergic contact dermatitis (ACD) is an inflammatory skin disease of great and steadily increasing importance as an occupational health problem. The disease is induced by chemicals and metal ions which penetrate the skin and form complexes with host proteins. This process is accompanied by a strong, allergen-induced inflammatory reaction and leads to the migration of allergen-carrying dendritic cells (DC) from the skin to regional lymph nodes, where they promote generation of allergen-specific T cells. The latter are the ultimate effector cells of the disease. Re-exposure to the causative agent leads to the recruitment of the T effector cells, which then elicit the typical skin inflammatory reaction at the site of contact. Although DC and effector T cells play a protagonistic role in the sensitization and elicitation phase of ACD, respectively, other cell types including keratinocytes, NK cells, mast cells and B cells contribute to the pathogenesis of the disease. In this review the authors summarize recent findings that identify stress responses and innate immune pathways triggered by contact allergens and review recent data regarding the adaptive T cell response. The new data were collected mainly from studies on contact hypersensitivity (CHS), the corresponding experimental mouse model of human ACD. The elucidation of the molecular events involved in contact allergen-induced innate responses will help to design new treatment strategies and may allow to develop predictive in vitro assays for the identification of contact allergens.