This review deals with emerging evidence of an association between systemic or local hypoxia and inflammation in a variety of diseases. The evidence points to new ways of treating inflammatory disorders or conditions such as certain cancers with intralesional hypoxia. Mammals have oxygen-sensing mechanisms that help them adapt quickly to hypoxia by increasing respiration, blood flow, and survival responses. If an inadequate supply of oxygen persists, additional mechanisms attempt to restore oxygenation or help the body adapt to hypoxia. 1 These other mechanisms rely on oxygen-sensing prolyl hydroxylases (PHDs), which hydroxylate prolines in the alpha subunit of the hypoxia-inducible transcription factor (HIF). This transcription factor is a heterodimer with two subunits: HIF-1α or HIF-2α and HIF-1β (or aryl hydrocarbon receptor nuclear translocator ARNT protein). HIF-1α is ubiquitous, whereas HIF-2α is restricted to certain tissues. 1 In this review, we show the ways . . .