Regardless of whether bacteria, yeast, invertebrates, or vertebrates are analyzed, every organism has the ability to sense and respond to reduced O 2 availability (hypoxia). As with other physiologic stimuli, a hypoxic stimulus/response can be categorized as either acute or chronic (Table 1). Acute responses occur over a time scale of seconds to minutes and involve the posttranslational modification of proteins or other macromolecules through reduction–oxidation reactions, phosphorylation–dephosphorylation, etc. Chronic responses occur over a time scale of minutes to hours and involve changes in gene expression.