The article by Wenger, Stiehl, and Camenisch reviews the integration of oxygen signaling at the consensus hypoxia response element (HRE). Oxygen availability regulates various physiological and pathophysiological processes, and the understanding of how cells adapt to insufficient oxygen supply (hypoxia) is crucial. The discovery of four oxygen-sensing protein hydroxylases has revealed their role in regulating the abundance and activity of hypoxia-inducible transcription factors (HIFs), which control the expression of at least 70 effector genes involved in hypoxic adaptation. In addition to its reactive nature in response to decreased tissue oxygenation, HIF is also proactively induced under normoxic conditions in response to growth stimuli, leading to higher oxygen consumption. Growth stimuli activate signaling pathways that influence HIF abundance and activity, including kinase pathways, redox-active substances, and reactive oxygen species (ROS). The final point of integration of these pathways is the HRE of effector genes, where HIF binds and induces gene expression. The article provides a comprehensive compilation of growth stimuli inducing HIF, HIF protein-protein interactions, and known HIF effector genes. The resulting consensus HRE sequence is useful for identifying novel HIF target genes, designing oxygen-regulated gene therapy, and predicting the effects of future drugs targeting the HIF system.The article by Wenger, Stiehl, and Camenisch reviews the integration of oxygen signaling at the consensus hypoxia response element (HRE). Oxygen availability regulates various physiological and pathophysiological processes, and the understanding of how cells adapt to insufficient oxygen supply (hypoxia) is crucial. The discovery of four oxygen-sensing protein hydroxylases has revealed their role in regulating the abundance and activity of hypoxia-inducible transcription factors (HIFs), which control the expression of at least 70 effector genes involved in hypoxic adaptation. In addition to its reactive nature in response to decreased tissue oxygenation, HIF is also proactively induced under normoxic conditions in response to growth stimuli, leading to higher oxygen consumption. Growth stimuli activate signaling pathways that influence HIF abundance and activity, including kinase pathways, redox-active substances, and reactive oxygen species (ROS). The final point of integration of these pathways is the HRE of effector genes, where HIF binds and induces gene expression. The article provides a comprehensive compilation of growth stimuli inducing HIF, HIF protein-protein interactions, and known HIF effector genes. The resulting consensus HRE sequence is useful for identifying novel HIF target genes, designing oxygen-regulated gene therapy, and predicting the effects of future drugs targeting the HIF system.