The induction of antigen-specific tolerance is essential to maintain immune homeostasis, control autoreactive T cells, prevent the onset of autoimmune diseases and achieve tolerance of transplants. Inflammation is a necessary process for eliminating pathogens, but can lead to serious deleterious effects in the host if left unchecked. Identifying the endogenous factors that control immune tolerance and inflammation is a key goal in the field of immunology. In the last decade, various neuropeptides that are produced by immune cells with potent anti-inflammatory actions were found to participate in the maintenance of tolerance in different immunological disorders.