Oxygen tensions play an important role in the outcome of infections. Oxygen is cidal or static for microorganisms that lack defenses against oxidants. Hyperoxia and hyperbaric oxygen exert antimicrobial effects by increasing the intracellular flux of reactive oxygen species. In bacteria, such species cause DNA strand breaks, degradation of RNA, inhibition of amino acid biosynthesis, and inactivation of membrane transport proteins. Oxygen tensions also affect the activity of antimicrobial agents. In general, hyperoxia potentiates while anaerobiosis decreases the activity of many antimicrobial drugs. With regard to host defenses, hyperoxia elevates oxygen tensions in infected tissues to levels that facilitate oxygen-dependent killing by leukocytes. Prolonged hyperoxia inhibits DNA synthesis in lymphocytes and impairs chemotactic activity, adherence, phagocytic capacity, and generation of the oxidative burst in polymorphonuclear leukocytes and macrophages.