Although it is generally believed that oxidative phosphorylation and adequate oxygenation are essential for life, human development occurs in a profoundly hypoxic environment and “normal” levels of oxygen during embryogenesis are even harmful. The ability of embryos not only to survive but also to thrive in such an environment is made possible by adaptations related to metabolic pathways. Similarly, cancerous cells are able not only to survive but also to grow and spread in environments that would typically be fatal for healthy adult cells. Many biological states, both normal and pathological, share underlying similarities related to metabolism, the electron transport chain, and reactive species. The purpose of Part I of this review is to review the similarities among embryogenesis, mammalian adaptions to hypoxia (primarily driven by hypoxia-inducible factor-1), ischemia-reperfusion injury (and its relationship with reactive oxygen species), hibernation, diving animals, cancer, and sepsis, with a particular focus on the common characteristics that allow cells and organisms to survive in these states.