Nickel allergy constitutes a serious health problem of modern societies. Hypersensitivity to this metal is found in 13% adults and 8% children. Risk factors for nickel allergy are: female gender and early exposure to nickel, e.g. piercing. Various mechanisms of inducing nickel allergy are possible, which is also reflected in the different clinical pictures. Nickel can induce allergic reaction in 3 different ways: 1) it binds to carrier protein in the extracellular space and subsequently is processed and presented by antigen presenting cell (APC) in the context of MHC class II molecule, which activates CD4+ lymphocytes, 2) Ni penetrates into the cell where it binds to intracellular proteins, and subsequently it is presented in the context of MHC class I molecule, which activates CD8+ lymphocytes, 3) Ni can "bridge" MHC molecule together with the TCR receptor on lymphocyte without actually filling the antigen-binding site, which is in analogy to superantigens. Both Th2/Tc2 (IL-4, IL-5, IL-13) and Th1/ Tc1 (IFNgamma) take their part in the development of contact allergy to nickel. The trafficking of the effector cells to target organs (where the inflammatory reaction actually takes place) is controlled by homing antigens and chemokine receptors that are expressed on their surface. The accumulation of effector cells in a target organ can determine the symptoms of nickel allergy (the skin, mucosa etc.). The acquisition of nickel tolerance is possibly dependent on the IL-10 secretion by specific lymphocytes.