The lung evolved to efficiently exchange oxygen and carbon dioxide between the external environment and circulating blood. Because it is an open conduit to the environment, the lung must also maintain tight barrier function, defend against inhaled toxins, and have tremendous repair capacity when injured. Creating, maintaining, and repairing the remarkably complex structure of the lung is controlled by genes that regulate cell autonomous functions and cell–cell interactions. However, many studies have now shown how perinatal environmental factors can also permanently modify lung development, thereby influencing long-term lung function and respiratory health. Environmental factors include oxygen at birth, nutrition and intrauterine growth restriction, prenatal and postnatal infections, ionizing radiation, ozone, tobacco smoke, and chemical toxins such as bisphenol A. Although perinatal influences are often considered detrimental to long-term respiratory health, how the lung responds to different levels of oxygen at birth suggests that its response to other influences may represent developmental changes in an organ evolutionarily designed to functionally adapt to its environment. Improving respiratory health as people age may therefore require a better understanding of how the perinatal environment plays a role in generating biologic fit and novelty.