Acute or chronic exacerbated hypoxic pulmonary hypertension (PH) is a frequent event in patients with severe respiratory failure, such as those presenting with acute exacerbation of chronic obstructive pulmonary disease (COPD) or with adult respiratory distress syndrome (ARDS). The increased pulmonary vascular tone may reduce right ventricular performance. This, in turn, may trigger a drop in cardiac output and in oxygen delivery; furthermore, in patients with ARDS, increased hypoxic vasoconstriction may enhance extravascular water accumulation. However, the increased pulmonary vascular tone acts as a natural defence mechanism on the level of the air-blood barrier and may reduce the intrapulmonary VA/Q mismatch. Systemic vasodilators may induce favourable hemodynamic effects in patients with a hypoxic PH and a reduced right ventricular performance. On the other hand, they may worsen gas exchange through a flow-diversion phenomenon (from normal lung units to units with a very low VA/Q relationship) or through inhibition of hypoxic vasoconstriction if PvO2 increases. Recently, nitric oxide (NO) has been recognized as an important endothelial factor with potent vasorelaxing properties; preliminary studies in patients with ARDS and in those with severe primary pulmonary hypertension have corroborated the power of this molecule in improving gas exchange and pulmonary hemodynamics without deleterious effects on the systemic circulation. However, further randomized controlled studies with NO are urgently needed in order to investigate the risk-benefit ratio and the prognostic significance of this promising new treatment. Until this occurs, patients with a hypoxic acute or chronic exacerbated PH should not be treated according to fixed criteria but on a reasonable case by case basis.