Abstract Background Inflammation is central to the initiation of immune responses and to the pathogenesis of many diseases such as allergic contact dermatitis (ACD). ACD is an inflammatory skin disease caused by low molecular weight organic chemicals and metal ions. The immune system plays a decisive role. After protein binding, the triggering chemicals act as contact allergens that are recognized by specific T cells. Before this can happen, however, the chemicals must trigger inflammation in the skin, without which the adaptive immune system in particular is not activated. Methods In recent years, the inflammatory mechanisms of contact allergy have been studied at the cellular and molecular level in vivo and in vitro. Results Contact allergens activate the innate immune system and additionally cellular stress responses, which in interaction are responsible for skin inflammation. In this context, inflammation is required for both initial sensitization and elicitation of ACD. Conclusion Skin inflammation in ACD is orchestrated by the interplay of the innate immune system and cellular stress responses.