OBJECTIVE: To synthesize available data related to the complex associations among viral infections, atopy, and asthma. DATA SOURCES: Key historical articles, articles highlighted in our recent review of most significant recent asthma advancements, and findings from several birth cohorts related to asthma and viral infections were reviewed. In addition, PubMed was searched for review articles and original research related to the associations between viral infection and asthma, using the search words asthma, viral infections, atopy, development of asthma, rhinovirus (RV), and respiratory syncytial virus (RSV). STUDY SELECTIONS: Articles were selected based on novelty and relevance to our topic of interest, the role of asthma and viral infections, and possible mechanisms to explain the association. RESULTS: There is a large body of evidence demonstrating a link between early viral infections (especially RV and RSV) and asthma inception and exacerbations. RV-induced wheezing is an important risk factor for asthma only when atopy is present, with much evidence supporting the idea that sensitization is a risk factor for early RV-induced wheezing, which in turn is a risk factor for asthma. RSV, on the other hand, is a more important risk factor for nonatopic asthma, with severe infections conferring greater risk. CONCLUSION: There are important differences in the development of atopic and nonatopic asthma, with several proposed mechanisms explaining the association between viral infections and the development of asthma and asthma exacerbations. Understanding these complex associations is important for developing asthma prevention strategies and targeted asthma therapies.