AbstractMetazoan life is dependent upon the utilization of O2 for essential metabolic processes and oxygen homeostasis is an organizing principle for understanding metazoan evolution, ontology, physiology, and pathology. Hypoxia‐inducible factor 1 (HIF‐1) is a transcription factor that is expressed by all metazoan species and functions as a master regulator of oxygen homeostasis. Recent studies have elucidated complex mechanisms by which HIF‐1 activity is regulated and by which HIF‐1 regulates gene expression, with profound consequences for prenatal development, postnatal physiology, and disease pathogenesis. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under: Physiology > Organismal Responses to Environment