Although early childhood wheeze is common, persistent asthma is less common. However, of those children who do progress to persistent asthma, lung function abnormalities and airway remodelling can already be seen early in life and can increase in magnitude with time. There has been a general expectation that early use of inhaled corticosteroid (ICS) could change the natural history of asthma if started in the young child with wheeze. Despite this expectation, the role of ICS therapy in altering the natural course of disease in children with emerging asthma is not well defined. Here we discuss the potential use of ICS therapy to alter the natural disease course in children at risk of persistent asthma (defined as wheeze and presence of airflow limitation or airway hyper-reactivity, or both). We present new information suggesting a more personalised treatment approach in which children might benefit from daily or intermittent ICS therapy. We also provide an overview of other emerging therapies that might be useful in disease modification for the wheezing young child at risk of persistent asthma.