Asthma is one of the most prevalent chronic diseases in developed countries, with steady increases in asthma prevalence evident, particularly in the last few decades. As genetic factors are unlikely to contribute to the rise in asthma prevalence, changes in lifestyle and exposure to environmental stimuli have been proposed to account for this trend. The ‘disappearing microbiota’ hypothesis postulates that major shifts in the human microbiome, resulting from dramatic lifestyle changes, account for the increase in asthma prevalence. In this context, persistent gastric colonization with the human-specific pathogen Helicobacter pylori has been negatively associated with the occurrence of asthma in epidemiological studies. In addition, experimental models of allergic airway disease revealed a direct link between infection with H. pylori and suppression of allergic airway disease through the induction of regulatory T cells. These and other new insights hold the promise of opening up new avenues toward the development of innovative, new strategies directed at asthma treatment and prevention.