The vasoactive intestinal peptide (VIP) is a neuropeptide belonging to the secretin/glucagon family of peptides, which exerts a wide spectrum of immunological functions controlling the homeostasis of immune system through different receptors expressed in various immunocompetent cells. In the last decade, VIP has emerged as a potent anti-inflammatory factor, which exerts its function by regulating the production of both anti- and pro-inflammatory mediators. In this sense, VIP has been proposed as a promising candidate, alternative to other existing treatments, for treating acute and chronic inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis and Crohn's disease. The present work reviews the involvement of the specific receptors and or different transduction pathways and transcription factors in the anti-inflammatory action of VIP, and their implication on its therapeutic effect on inflammatory/autoimmune disorders.