Asthma is characterised by airway hyper-responsiveness and remodelling, and there is mounting evidence that alterations in the phenotype of airway smooth muscle (ASM) play a central role in these processes. Although the concept that dysregulation of ASM Ca 2+ homeostasis may underlie at least part of these alterations has been around for many years, it is only relatively recently that the availability of ASM biopsies from subjects with mild and moderate asthma has allowed it to be properly investigated. In this article, critical components of the pathobiology of asthmatic ASM, including contractile function, proliferation, cell migration and secretion of proinflammatory cytokines and chemokines, are reviewed and related to associated changes in ASM Ca 2+ homeostasis. Based on this evidence, it is proposed that a unifying mechanism for the abnormal asthmatic phenotype is dysregulation of Ca 2+ homeostasis caused at least in part by a downregulation in expression and function of sarcoendoplasmic Ca 2+ ATPases (SERCAs).Asthma is a chronic inflammatory disease which is characterised by widespread structural changes in the airways (airway remodelling), encompassing epithelial dysfunction, mucous gland hypertrophy, deposition of extracellular matrix (ECM) and changes in airway smooth muscle (ASM) phenotype. 1 ASM from patients with asthma exhibits enhanced contractile activity, 2e4 as well as enhanced proliferation, migration and secretion of proinflammatory cytokines.5e8 This article reviews critical components of asthmatic ASM pathobiology and suggests that a unifying mechanism for the abnormal asthmatic phenotype is dysregulation of Ca 2+ homeostasis caused at least in part by a downregulation in expression of sarcoendoplasmic Ca 2+ ATPases (SERCAs).