Severe respiratory failure results from large right to left shunting. In the newborn, both intrapulmonary and/or extrapulmonary shunting may cause severe respiratory failure. Right to left extrapulmonary shunting is associated with pulmonary hypertension (PPHN). Management depends on the main mechanism of the respiratory failure. Intrapulmonary shunting requires optimizing lung recrutment, whereas vascular recrutment is required to decrease extra-pulmonary shunting. Analysis of anamnesis, clinical examination, chest X-ray, and echocardiography allows distinguishing the mechanism of the respiratory failure. In case of PPHN, favorizing factors such as acidosis, stress, lung over distension, and polyglobuly should be treated. Inhaled NO is recommended in the treatment of PPHN after optimizing lung volume.