Sensing and responding to fluxes in oxygen tension is perhaps the single most important variable in physiology, and animal tissues have developed a number of essential mechanisms to cope with the stress of low physiological oxygen levels, or hypoxia. Among these coping mechanisms is the response mediated by the hypoxia-inducible transcription factor, or HIF-1. HIF-1 is an essential component in changing the transcriptional repertoire of tissues as oxygen levels drop, and could prove to be a very important target for drug development, as treatments evolve for diseases, such as cancer, heart disease and stroke, in which hypoxia is a central aspect.