This area of scientific investigation is less well known to both the lay and professional reader, but it has profound practical importance. It concerns how our bodies handle oxygen in health and disease and adapt to low oxygen states. One issue of the Journal of Molecular Medicine is entirely devoted to hypoxia (low oxygen) and human disease. It contains papers encompassing a range of conditions including cardiovascular, gastrointestinal, kidney and lung diseases, cancer and more. The focus here is on one paper that extensively reviews the regulation of oxygen in immunity and the response to infection. This is particularly important because there seem to be many clinicians who assume that increasing oxygen saturation in the locale of an infection helps to get rid of it (through oxidative damage to the pathogen and healthier surrounding tissues). Due to the research over the past several years on the powerful and important role of hypoxia inducible factor (HIF) we can understand that this is incorrect. “The hypoxia-inducible transcription factor (HIF-1α) is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress.” It exerts powerful control over the white blood cells that respond to infection: “HIF-1α has been discovered to function as a global regulator of macrophage and neutrophil inflammatory and innate immune functions.” They refer to HIF-1α as “a master regulator of innate immunity.” This is a fascinating review with references to many other studies if you care to read it, but the main point I want to bring to your attention is this: “A paradoxical result of these findings is that, due to HIF-1α activation, macrophages actually phagocytose and kill bacteria better under hypoxic conditions than they do under normoxic conditions.” This means white blood cells kill bacteria more effectively in a low oxygen environment than they do when oxygen in that location is normal. They go on to explain its role in viral and parasitic infections and the progression of viral infections to cancer. They go on to conclude: “The proof-of-principle experiments described suggest further exploration of HIF-1α augmentation to boost innate defense function. This may be of interest as a therapeutic strategy in infectious disease conditions complicated by antibiotic resistance or compromised host immunity.” Certainly this is a complex system and much more could be said, but the practical message is this: think each case through very carefully before advising or receiving oxidative therapies for infection.