The traditional view of the pathophysiology of asthma is that its characteristic features are secondary to a major allergic or immunological dysfunction. However, this does not explain intrinsic asthma, which can occur in the absence of atopy. An alternative view is that an abnormality in the airway smooth muscle cell, which is capable of producing inflammatory, immunological and growth factors as well as molecules, which facilitate interaction with inflammatory cells, is the primary or instigating event. Evidence is rapidly accumulating that the smooth muscle is abnormal, in that it proliferates faster, produces more chemokines and cytokines as well as a different profile of extracellular matrix proteins than its non-asthmatic counterpart. These abnormalities may arise from altered calcium homoeostasis leading to increased mitochondrial biogenesis and/or decreases in the levels of key transcription factors such as CCAAT enhancer binding protein−α. Conditions under which smooth muscle is ablated, such as bronchial thermoplasty, may help us to understand more about the contribution of an airway smooth muscle dysfunction to asthma aetiology.