Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early-life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early-life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies.