Several neuropeptides have now been localized to nerves in human airways and have marked effects on airway smooth muscle tone, bronchial blood flow, microvascular leakage, and airway secretions. There is mounting evidence that they may act as neurotransmitters of nonadrenergic, noncholinergic nerves and may be co-transmitters of classic autonomic nerves. Vasoactive intestinal peptide and the related peptide histidine methionine are potent relaxants of human airways in vitro, yet their effects in vivo are disappointing because of problems in delivery. Sensory neuropeptides such as substance P, neurokinins A and B, and calcitonin gene-related peptide may be involved in neurogenic inflammatory reactions in asthma. Although there have been no clinical benefits from these discoveries, in the future the development of agents that interfere with or mimic neuropeptide effects may offer novel therapeutic approaches to airway diseases such as asthma.