Asthma is a chronic inflammatory disease, with hyper-responsive bronchoconstriction and airway remodelling, leading to extensive airway narrowing. The regulation of airway responsiveness and inflammation by endogenous hydrogen sulfide (H(2)S) during the pathogenic development of asthma has been suggested. Hydrogen sulfide can be produced in the lung and airway tissues via the actions of two H(2)S-generating enzymes, cystathionine β-synthase (CBS) and/or cystathionine γ-lyase (CSE). The abnormal metabolism and function of H(2)S have been reported in experimental animals with asthma, especially ovalbumin-induced rat or mouse models. In patients with asthma, serum H(2)S levels are significantly reduced. Supplementation with exogenous H(2)S has been shown to mitigate the severity of asthma in experimental animals. It is hypothesized that decreased H(2)S production in the lung and airway tissues may be used as an early detection biomarker, and H(2)S-based therapy would represent a new treatment strategy for asthma. Major challenges for establishing the diagnostic and treatment values of H(2)S include the differential expression of CSE and CBS along the airway and their changes during asthma, the effects of H(2)S on bronchoconstriction and airway remodelling, as well as the underlying mechanisms, and the detection of the changes in H(2)S levels in airway tissues and in exhaled air.