Childhood asthma develops from a complex interaction among host and environmental factors in early life. Birth cohort studies have provided valuable insight into asthma risk factors and the natural history of wheezing and asthma through childhood and beyond. Early life aeroallergen sensitization and wheezing illnesses associated with virus and bacterial infections have been identified as pivotal risk factors for asthma inception. Recently, focus has turned toward protective factors that promote lung health in children. Studies in a variety of environments, including farms and urban communities, suggest that diverse exposures to microbes in early life lead to a lower risk of allergy and asthma in childhood. The mechanisms underlying how these exposures and the gut and airway microbiomes alter the host response to allergens and viruses are of interest and an area of ongoing study. Longitudinal follow up of birth cohorts in diverse environments worldwide will continue to provide critical knowledge about the factors that impact the natural history of asthma.