Results from birth cohort and cross-sectional studies of young children with wheezing have uncovered strong associations between both lung function and immune responses in early life and the subsequent development of persistent wheezing and chronic airway obstruction up to mid-adulthood. It is now apparent that the pattern of bronchial hyperresponsiveness, deficits in lung function, and structural airway remodeling that are characteristic of asthma may be already established during the preschool years in most patients. Interactions between acute viral infections, especially those due to rhinovirus and respiratory syncytial virus, and exposure to perennial aeroallergens may induce persistent alterations in immune responses and airway function in susceptible subjects. Similarly, deficits in airway function present shortly after birth predict airflow limitation in early adult life, which in turn is a strong predisposing factor for chronic obstructive pulmonary disease. The fact that these alterations are more likely to occur during early life and even in utero than later during childhood suggests that there a developmental window of susceptibility during which exposures can disrupt normal growth trajectories. Novel strategies for primary prevention of chronic respiratory diseases will be based on the identification of the genetic and environmental factors that interactively cause these disruptions.