NADPH oxidase is classically regarded as a key enzyme of neutrophils, where it is involved in the pathogenic production of reactive oxygen species. However, NADPH oxidase-like enzymes have recently been identified in non-neutrophil cells, supporting a separate role for NADPH-oxidase derived oxygen species in oxygen sensitive processes. This article reviews the current literature surrounding the potential role of NADPH oxidase in the oxygen sensing processes which underlie hypoxic pulmonary vasoconstriction, systemic vascular smooth muscle proliferation, carotid and airways chemoreceptor activation, erythropoietin gene expression, and oxytropic responses of plant cells.