The prognosis of acute pulmonary embolism (PE) is mainly related to the clinical presentation and circulatory state of the patient: the therapeutic strategy is consequently different, ranging from an aggressive treatment in patients in life-threatening clinical conditions to a "stabilization" treatment in those hemodynamically stable. Since the majority of PE patients are clinically stable, a well conducted anticoagulant therapy, either with unfractionated or low-molecular-weight heparins together with a vitamin K antagonist, is sufficient to stop thrombus extension, to minimize the risk of recurrent embolism and prevent mortality. In about 15-20% of cases presenting with clinical instability of variable severity, prompt intravenous thrombolysis with a short-acting compound often represents a life-saving treatment and should be the first-line approach. In normotensive patients with right ventricular dysfunction at echocardiography, who represent about 30% of PE patients, the debate regarding the optimal therapy is still open and further studies are required to document a clinically relevant improvement in the benefit-risk ratio of thrombolytic agents over heparin alone: young people, with a very low risk of bleeding and a concomitant reduction of cardiopulmonary reserve might be the best candidates to systemic thrombolysis. In any case such patients should be admitted to an intensive care unit to monitor the clinical status for at least 48-72 hours and detect signs of possible hemodynamic worsening. Mechanical thrombectomy, either percutaneous or surgical, are ancillary procedures and should be reserved to a minority of highly compromised patients who are unable to receive thrombolysis.