Peptidergic neuromediators have gained importance in the field of respiratory physiology and pathophysiology due to the characterisation of numerous pulmonary effects in the past years. With regard to the multitude of mediators, the neuropeptide vasoactive intestinale polypeptide (VIP) plays a special role as it exerts potent anti-inflammatory and immunomodulatory effects. Neurophysiologically the peptide has been attributed to the family of the inhibitory non-adrenergic non-cholinergic (i-NANC) neuromediators of the pulmonary innervation. VIP-containing nerve fibres are localized in the airway and vascular smooth muscle layers of trachea and bronchi in the human respiratory tract. Apart from strong vasodilatory effects, the peptide also shows a high bronchodilatory potency. In a large number of respiratory diseases VIP may play a pathophysiological role. In this respect, increased levels of VIP have been demonstrated for inflammatory diseases of the upper and lower airways and the peptide may also play a role in pulmonary hypertension. Due to its fast enzymatic cleavage, VIP-based therapies have not been used in routine therapy so far. Also, the use of synthetic VIP-agonists did not lead to an improved outcome in patients with bronchial asthma if compared to classical drugs. However, recent data from animal experiments indicate potent immunomodulatory effects which suggest a future use of this mediator and its agonists in the therapy of immune diseases.