As a consequence of aerobic life, an organism must deal with the continuous generation of reactive oxygen species (O2-, H202, .OH) as byproducts of metabolism and defend itself against the harm that these can do to cellular macromolecules. Organisms protect themselves from such damage with both enzymatic and nonenzymatic antioxidant defenses. However, the reperfusion injuries noted after ischemic insult in mammalian organs and ascribed to a burst of reactive oxygen species produced when oxygenated blood is reintroduced demonstrate that the antioxidant defenses of many organisms can be overwhelmed, Although unusual among most mammals, many organisms routinely experience wide variation in oxygen availability to their tissues due to factors such as environmental oxygen lack, breath-hold diving, extracellular freezing, or apnoeic breathing patterns in arrested metabolic states. In recent studies using various animal models (anoxia-tolerant turtles, freeze-tolerant snakes and frogs, estivating snails) our laboratory has explored the adaptations of antioxidant defenses that allow such organisms to deal with rapid changes in tissue oxygenation with little or no accumulation of damage products. The key to successful transitions in several systems is the induction, during the oxygen-limited state, of elevated activities of antioxidant and associated enzymes, such as catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase, so that damage during the reintroduction of oxygen (such as lipid peroxidation) is minimized. However, animals that are excellent facultative anaerobes, such as freshwater turtles, appear to deal with potential of oxidative stress during the anoxic-aerobic transition by maintaining constitutively high antioxidant defenses (e.g. enzyme activities similar to those of mammals and much higher than those of anoxia-intolerant lower vertebrates) that can readily accommodate the burst of reactive oxygen species generation when breathing is renewed.