PURPOSE OF REVIEW: This article presents recent findings and perspectives on the relationship between early-life respiratory infections and asthma inception, and discusses emerging concepts on strategies that target these infectious agents for asthma prevention. RECENT FINDINGS: Cumulative evidence supports the role of early-life viral infections, especially respiratory syncytial virus and human rhinovirus, as major antecedents of childhood asthma. These viruses may have different mechanistic roles in the pathogenesis of asthma. The airway microbiome and virus-bacteria interactions in early life have emerged as additional determinants of childhood asthma. Innovative strategies for the prevention of these early-life infections, or for attenuation of acute infection severity, are being investigated and may identify effective strategies for the primary and secondary prevention of childhood asthma. SUMMARY: Early-life infections are major determinants of asthma development. The pathway from early-life infections to asthma is the result of complex interactions between the specific type of the virus, genetic, and environmental factors. Novel intervention strategies that target these infectious agents have been investigated in proof-of-concepts trials, and further study is necessary to determine their capacity for asthma prevention.