Asthma is an airway disease highly prevalent in westernized countries and of unknown etiology. Often, asthma is associated with atopy, but not all atopic individuals have asthma. Some patients with asthma outgrow symptoms, whereas many others acquire asthma later in life. Still other patients suffer from asthma their entire life. How can we explain these different patterns? It may be that asthma should be regarded as the clinical manifestation of a group of diseases with similar pathology due to a common factor. In this Pulmonary Perspective, we propose that an aberrant phenotype of airway smooth muscle (ASM) cells could be sufficient to explain the pathology of asthma. We will argue an abnormal ASM cell is a prerequisite to the development of asthma. Our postulate is that inadequate levels of C/EBPα, a protein that is pivotal for the suppression of both inflammation and proliferation responses, confer on ASM cells an activated phenotype that is more susceptible to mitogenic and contractile stimuli.