Hypoxia causes a cascade of activity from the level of the individual down to the regulation and function of the cell nucleus. Prolonged periods of low oxygen tension are a core feature of several disease states. Advances in the study of molecular biology have begun to bridge the gap between the cellular response to hypoxia and physiology. Hyperbaric oxygen therapy is a treatment for hypoxic- and inflammatory-driven conditions, in which patients are treated with 100% oxygen at pressures greater than atmospheric pressure. This review discusses hypoxia, the physiologic changes associated with hypoxia, the responses that occur in the cells during hypoxic conditions, and the role that hyperbaric oxygen therapy can play as part of the treatment for many patients suffering from diseases with underlying hypoxia.