In human physiology, nitrite anions were long considered metastable intermediates in an irreversible oxidation cascade from nitric oxide (NO) to nitrate. A growing body of experimental and clinical observations attest that endogenous nitrite in the vascular tree is reduced to NO under hypoxic conditions. The phenomenon causes hypoxic responses like vasodilation, downregulation of mitochondrial respiration, and cytoprotection after ischemic insult. It is noteworthy that significant quantites of NO are released already at physiological nitrite levels, i.e. without administration of exogenous nitrite. We will discuss several pathways for hypoxic reduction of nitrite. It is mediated by human proteins like xanthine oxidase, eNOS, deoxy-myoglobin or deoxy-hemoglobin. We will discuss the role played by the local oxygen concentration in tissues like the vascular endothelium.