Acute right ventricular (RV) failure and impaired gas exchange (mainly hypoxaemia) can be two important issues clinicians are confronted with in patients with acute pulmonary embolism. An acute increase in RV afterload due to mechanical obstruction and vasoconstriction is the crucial factor starting a cascade with compensatory mechanisms, RV dilatation, RV ischaemia, and inflammation ultimately leading to RV dysfunction/failure. On the other hand, vascular occlusion leads to redistribution of pulmonary perfusion to regions with relative overperfusion causing profound hypoxaemia. Less commonly, shunting occurs due to atelectasis or due to opening of a patent foramen ovale, causing refractory hypoxaemia. Understanding these mechanisms is crucial in making the right treatment decisions when faced with a patient with acute pulmonary embolism and haemodynamic or respiratory instability.