Asthma is one of the most common diseases in the world, resulting in a substantial burden of disease. Although rates of deaths due to asthma worldwide have reduced greatly over the past 25 years, no available therapeutic regimens can cure asthma, and the burden of asthma will continue to be driven by increasing prevalence. The reasons for the increase in asthma prevalence have not been defined, which limits the opportunities to develop targeted primary prevention measures. Although associations are reported between a wide range of risk factors and childhood asthma, substantiation of causality is inherently difficult from observational studies, and few risk factors have been assessed in primary prevention studies. Furthermore, none of the primary prevention intervention strategies that have undergone scrutiny in randomised controlled trials has provided sufficient evidence to lead to widespread implementation in clinical practice. A better understanding of the factors that cause asthma is urgently needed, and this knowledge could be used to develop public health and pharmacological primary prevention measures that are effective in reducing the prevalence of asthma worldwide. To achieve this it will be necessary to think outside the box, not only in terms of risk factors for the causation of asthma, but also the types of novel primary prevention strategies that are developed, and the research methods used to provide the evidence base for their implementation. In the interim, public health efforts should remain focused on measures with the potential to improve lung and general health, such as: reducing tobacco smoking and environmental tobacco smoke exposure; reducing indoor and outdoor air pollution and occupational exposures; reducing childhood obesity and encouraging a diet high in vegetables and fruit; improving feto-maternal health; encouraging breastfeeding; promoting childhood vaccinations; and reducing social inequalities.