Schwann cells are the myelinating glial cells of the peripheral nervous system that support and ensheath axons with myelin to enable rapid saltatory signal propagation in the axon. Immunocompetence, however, has only recently been recognized as an important feature of Schwann cells. An autoimmune response against components of the peripheral nervous system triggers disabling inflammatory neuropathies in patients and corresponding animal models. The immune system participates in nerve damage and disease manifestation even in non-inflammatory hereditary neuropathies. A growing body of evidence suggests that Schwann cells may modulate local immune responses by recognizing and presenting antigens and may also influence and terminate nerve inflammation by secreting cytokines. This review summarizes current knowledge on the interaction of Schwann cells with the immune system, which is involved in diseases of the peripheral nervous system.