Systemic contact dermatitis (SCD) is a skin inflammation occurring in a patient after systemic administration of a hapten, which previously caused an allergic contact skin reaction in the same person. Most frequently, hypersensitivity reactions typical for SCD occur after absorption of haptens with food or inhalation. Haptens occur mainly in the forms of metals and compounds present in natural resins, preservatives, food thickeners, flavorings and medicines. For many years, several studies have been conducted on understanding the pathogenesis of SCD in which both delayed type hypersensitivity (type IV) and immediate type I are observed. Components of the complement system are also suspected to attend there. Helper T cells (Th) (Th1 and Th2), cytotoxic T lymphocytes (Tc), and NK cells play a crucial role in the pathogenesis of SCD. They secrete a number of pro-inflammatory cytokines. In addition, regulatory T cells (Tregs) have an important role. They control and inhibit activity of the immune system during inflammation. Tregs release suppressor cytokines and interact directly with a target cell through presentation of immunosuppressive particles at the cell surface. Diagnostic methods are generally the patch test, oral provocation test, elimination diet and lymphocyte stimulation test. There are many kinds of inflammatory skin reactions caused by systemic haptens’ distribution. They are manifested in a variety of clinical phenotypes of the disease.