Inhaled nitric oxide (iNO) has been extensively used in the treatment of severe hypoxaemic respiratory failure and/or pulmonary hypertension. Although the majority of studies have almost consistently demonstrated a beneficial effect on oxygenation and a reduction in pulmonary artery pressures, none of the randomised trials have reported a reduced mortality using iNO on patients with severe respiratory failure. In neonates with severe respiratory failure and pulmonary hypertension, however, iNO can reduce the need of extracorporal membrane oxygenation. Prior to using iNO on adult patients we suggest other measures to be taken (i.e. optimising ventilator settings, ventilation in prone position).