The peripheral nervous system (PNS) is the target for a heterogenous immune attack mediated by T-cells, B-cells, and macrophages. The interaction of the humoral and cellular immune system with the structural components in the peripheral nervous system may determine the extent of inflammation and possibly repair mechanisms. The animal model experimental autoimmune neuritis (EAN) allows detailed study of the various effector pathways and tests novel therapeutic strategies in vivo. Unexpectedly, involvement of the immune system is also found in animal models for inherited neuropathies and in its human counterpart Charcot-Marie-Tooth (CMT) disease, suggesting an autoimmune reaction triggered by the genetically determined demyelinating disorder. A better understanding of immune regulation and its failure in the peripheral nervous system may help to develop more specific and more effective immunotherapies.