© 2019 Elsevier Inc. Fetal development occurs in a relatively hypoxemic environment, and birth represents significant oxidative stress. Premature infants are disadvantaged by a lack of maternal antioxidant transfer and impaired endogenous antioxidant responses. O2 metabolism is essential for life and its biochemical reactions are dynamic, compartmentalized, and difficult to characterize in vivo. There is a growing appreciation for the role of reactive oxygen species in nonpathologic processes, including regulation of cell signaling and mitochondrial function. There are several gaps in the knowledge about the role of reactive oxygen species in normal development and how oxidative stress alters normal signaling and subsequent development.