Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion ratio distribution towards shunt or low ventilation/perfusion zones. Pharmacological modification of pulmonary blood flow distribution improving ventilation/perfusion ratio should correct hypoxia. The development of inhaled nitric oxide therapy had confirmed this concept, but with a relatively high proportion of ‚non responders‚. Then development of other drugs used alone or in association with nitric oxide may reinforce the benefit of nitric oxide. This has been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic pulmonary vasoconstriction. Using inhaled nitric oxide in combination with almitrine, several studies in adult respiratory distress syndrome or acute lung injury patients have shown spectacular results in term of PaO2and pulmonary shunt reduction. Moreover, the proportion of responders to this combination seems largely great than those observed for each drug alone. In conclusion, pulmonary blood flow manipulation improving ventilation/perfusion mismatching is one of the major strategies to correct severe hypoxia. Curr Opin Anaesthesiol 12:37-42.