The relationship between infections, immune development, and preschool recurrent wheezing and asthma is complex and multifaceted. Respiratory syncytial virus (RSV) and rhinovirus (RV) are significant early-life triggers for wheezing, with differing immunologic and genetic associations. RV, especially RV-C, has been closely linked to asthma development, particularly allergic asthma. RSV wheezing illnesses can identify susceptible children and are linked to nonallergic asthma. Ongoing studies using broader RSV prevention (vaccines, mAbs) in full-term infants may further clarify these relationships. Both RSV and RV infections are associated with changes in bacterial abundance. The timing of these changes and the bacterial strains that are altered are likely important factors in asthma development that are continually being investigated. Beyond viral triggers, asthma and recurrent wheeze in preschoolers result from a complex interplay of microbial (urban vs rural living), environmental (eg, air pollution levels and diet) and host immune factors. Strategies focusing on microbiome modulation (eg, bacterial lysate ingestion), pollution reduction, increasing biodiversity, and nutritional support (eg, vitamin D) may offer promising paths for prevention and improved management.