Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, and individuals with this disease respond to a range of physiological and chemical insults that are otherwise innocuous to healthy subjects, suggesting that the mechanisms underlying this phenomenon are characteristic of the asthma phenotype. BHR can be increased following exposure to environmental allergens in suitably sensitized individuals, pollutants, and certain viruses and can also be exacerbated by exposure to certain drugs, including nonsteroidal anti-inflammatory agents and beta-blockers. Although beta2-agonists administered acutely remain the treatment for the symptoms of asthma, paradoxically, regular treatment with these drugs can result in an increase in BHR, and this has been suggested to contribute to the increase in asthma morbidity and mortality that has been reported by numerous investigators. This article highlights our current understanding of this phenomenon and examines the potential mechanisms responsible for this effect.