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Acute pulmonary embolism (PE) requires rapid diagnosis and early and appropriate treatment, often under conditions of hemodynamic instability. The therapeutic strategy should optimally integrate the therapeutic arsenal in a multidisciplinary but unitary approach.The short list of the major uncertainties associated with acute PE should include limited general public awareness on venous thromboembolism, acute hemodynamic support not based on evidence from randomized clinical trials, with few updates lately, mainly linked to extracorporeal membrane oxygenation, thrombolytic therapy having firm indications only in high-risk PE, without clear strategies for particular clinical situations (ie, stroke, tumors, thrombi in transit, and cardiac arrest), using old therapeutic agents with old administration regimens, lack of evidence from large-volume trials on the optimal interventional approach, and relatively imprecise indications for surgical treatment.We reviewed current data on the diagnosis and therapeutic approach of acute PE.A collaborative idea has been reached: apply the multidisciplinary expertise of a rapid response heart team to patients with PE in Pulmonary Embolism Response Teams. Optimization of acute hemodynamic support involves the cautious use of volume expansion; diuretic treatment may provide early improvement in normotensive patients with acute PE and RV failure, and during massive PE, we may use the venoarterial extracorporeal membrane. Until new data accumulate, rescue reperfusion should be performed only if hemodynamic decompensation develops despite adequate anticoagulation. Only EkoSonic catheter is approved by the FDA in the interventional treatment of acute PE, without the routine use of retrievable inferior vena cava filters. Outcomes of pulmonary embolectomy after an early triage of patients with hemodynamically unstable PE are acceptable. In selected low-risk patients, an ambulatory treatment of PE with DOAC is effective and safe.Nowadays, evidence and ideas have been gathered that can significantly improve the outcome of patients with PE with varying degrees of severity, remaining to demonstrate the cost-effectiveness of this advanced therapeutic approach.