The infant’s developing immune response is central to establishing a balanced system that reacts appropriately to infectious stimuli, but does not induce altered disease states with potential long-term sequelae. Respiratory syncytial virus may alter the immune system, affecting future responses. Early infection may have direct effects on the lung itself. Other early life processes contribute to the development of immune responses including assembly of the microbiome, which seems to have a particularly important role for establishing the immune environment. This review covers studies that have set up important paradigms and discusses recent data that direct research toward informative hypotheses.