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Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention.This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections. The combined influence and interaction of early life viral wheezing and aeroallergen sensitization is important, with allergic sensitization preceding the onset of viral wheeze. Lastly, we review recent data from longitudinal studies regarding the development of irreversible airway obstruction and its impact on the natural history of asthma.The development of asthma remains complex and incompletely understood. There is interplay between genetic predisposition and environmental exposures, including allergens and microbes. Interventions aimed at these risk factors during the preschool years may prevent the longitudinal course of asthma progression to irreversible airway obstruction.