Since O(2) is the bare necessity for multicellular organisms, they develop multiple protective mechanisms against hypoxia. Mammals will adapt to hypoxia in short and long terms. The short-term responses include enhancement of the respiratory and cardiac functions, adrenaline secretion from adrenal medullary cells, and pulmonary vasoconstriction, whereas the long-term response is the increase in erythropoietin production with the consequent increase in red blood cells. Although much work has been done to elucidate molecular mechanisms for O(2)-sensing for the last ten years, the majority of the mechanisms remain unclear. We will review mechanisms proposed for hypoxia detection in carotid body type I cells, pulmonary artery smooth muscle, adrenal medullary cells, and liver cells, with the special focus on adrenal medullary cells.