Nitric oxide (NO) is a unique molecule in the human body and is responsible for normal neurologic function, vasodilator tone and modulation of the inflammatory response. Massive endogenous release of NO appears to play a central role in sepsis and the systemic inflammatory response syndrome. Inhaled NO (1-80 ppm) can markedly attenuate pulmonary vasoconstriction and improve hypoxemia due to ventilation perfusion mismatch.However, excessive doses of inhaled NO exacerbate acute inflammation and induce lung injury by the action of NO itself or its reactive metabolites. Thus far, its use has received FDA approval only for persistent pulmonary hypertension of the newborn (PPHN). However, on an investigational basis it can be used in lung and heart transplantation and LVAD insertion. Although prospective studies have not demonstrated that inhaled NO improves outcome in ARDS, its use as a component of an algorithmic approach has achieved an impressive survival rate. Other conditions in which inhaled NO shows promise include primary pulmonary hypertension, sickle cell Anemia and hypoxic chronic obstructive lung disease.