Exposure to a class of airborne pollutants known as particulate matter (PM) is an environmental health risk of global proportions. PM is thought to initiate and/or exacerbate respiratory disorders, such as asthma and airway hyper-responsiveness and is epidemiologically associated with causing death in the elderly and those with pre-existing respiratory, or cardiopulmonary disease. Plausible mechanisms of action to explain PM inflammation and its susceptible sub-population component are lacking. This review describes a series of published studies which indicate that PM initiates airway inflammation through sensory neural pathways, specifically by activation of capsaicin-sensitive vanilloid (e.g. VRI) irritant receptors. These acid-sensitive receptors are located on the sensory C nerve fibers that innervate the airways as well as on various immune and non-immune airway target cells. The activation of these receptors results in the release of neuropeptides from the sensory terminals that innervate the airways. Their interactions with airway target cells, result in signs of inflammation (e.g. bronchoconstriction, vasodilation, histamine release, mucous secretion etc.). Our data have linked the activation of the VR1 receptors to the surface charge carried on the colloidal particulates which constitute PM pollution. Related studies have examined how genetic and non-genetic factors modify the sensitivity of these irritant receptors and enhance the inflammatory responsiveness to PM. In summary, this review proposes a mechanism by which neurogenic elements initiate and sustain PM-mediated airway inflammation. Although neurogenic influences have been appreciated in normal airway homeostasis, they have not, until now, been associated with PM toxicity. The sensitivity of the sensory nervous system to irritants and its interactions with pulmonary target tissues, should encourage neuroscientists to explore the relevance of neurogenic influences to toxic disorders involving other peripheral target systems.