Schwann cells are the myelinating glial cells of the peripheral nervous system and establish myelin sheaths on large caliber axons in order to accelerate their electrical signal propagation. Apart from this well described function, these cells revealed to exhibit a high degree of differentiation plasticity as they were shown to re- and dedifferentiate upon injury and disease as well as to actively participate in regenerative- and inflammatory processes. This review focuses on the crosstalk between glial- and immune cells observed in many peripheral nerve pathologies and summarizes functional evidences of molecules, regulators and factors involved in this process. We summarize data on Schwann cell's role presenting antigens, on interactions with the complement system, on Schwann cell surface molecules/receptors and on secreted factors involved in immune cell interactions or para-/autocrine signaling events, thus strengthening the view for a broader (patho) physiological role of this cell lineage.